This invention is in the field of antiinflammatory pharmaceutical agents and specifically relates to compounds, compositions and methods for treating inflammation and inflammation-associated disorders, such as arthritis.
Prostaglandins play a major role in the inflammation process and the inhibition of prostaglandin production, especially production of PGG2, PGH2 and PGE2, has been a common target of antiinflammatory drug discovery. However, common non-steroidal antiinflammatory drugs (NSAIDs) that are active in reducing the prostaglandin-induced pain and swelling associated with the inflammation process are also active in affecting other prostaglandin-regulated processes not associated with the inflammation process. Thus, use of high doses of most common NSAIDs can produce severe side effects, including life threatening ulcers, that limit their therapeutic potential. An alternative to NSAIDs is the use of corticosteroids, which have even more drastic side effects, especially when long term therapy is involved.
Previous NSAIDs have been found to prevent the production of prostaglandins by inhibiting enzymes in the human arachidonic acid/prostaglandin pathway, including the enzyme cyclooxygenase (COX). The recent discovery of an inducible enzyme associated with inflammation (named xe2x80x9ccyclooxygenase-2 (COX-2)xe2x80x9d or xe2x80x9cprostaglandin G/H synthase IIxe2x80x9d) provides a viable target of inhibition which more effectively reduces inflammation and produces fewer and less drastic side effects.
The references below that disclose antiinflammatory activity, show continuing efforts to find a safe and effective antiinflammatory agent. The novel imidazoles disclosed herein are such safe and also effective antiinflammatory agents furthering such efforts. The invention compounds are found to show usefulness in vivo as antiinflammatory agents with minimal side effects. The substituted imidazoles disclosed herein preferably selectively inhibit cyclooxygenase-2 over cyclooxygenase-1.
Diaryl oxazoles have been described in WO patent publication WO94/27980 as having antiinflammatory activity. Substituted 4,5-diarylimidazoles have been described in WO95/00501 and in copending U.S. application Ser. No. 08/281,903.
2-Alkylimidazoles have been described as having angiotensin II activity. For example, see U.S. Pat. No. 5,185,351 and WO 91/00277.
U.S. Pat. No. 5,207,820 to Wriede et al. describes 1-arylimidazole carboxylic esters as herbicide safeners. Specifically, ethyl [1-[2,6-dinitro-4-(methylsulfonyl)phenyl]-2-methyl-1H-imidazol-3-yl]carboxylate is described.
WO 93/14082, published Jul. 22, 1993, describes 1-pyridyl-2-phenyl-imidazole derivatives for the treatment of interleukin-1 mediated diseases. 1-(4-Pyridyl)-2-(4-fluorophenyl)-4-methylimidazole is described. WO 95/02591, published Jan. 26, 1995, describe tri-substituted imidazoles for the treatment of cytokine mediated diseases.
U.S. Pat. No. 3,487,087, to Sarett et al., describes a method of nitration of imidazoles and specifically 1-methyl-2-[4-(methylsulfonyl)phenyl]-5-nitroimidazole.
U.S. Pat. No. 5,112,532, to Ninomiya et al., describes imidazoles as an organic non-linear optical material. Specifically, 4-(4-hydroxyphenyl)-2-[2-formyl-4-(methylsulfonyl)phenyl]imidazole is described.
U.S. Pat. Nos. 3,682,949 and 3,719,759, to Sarett et al., describe 2-aryl-nitroimidazoles as agents for the treatment of parasites and bacteria. Specifically, 1-(2-hydroxyethyl)-2-(4-sulfonamidophenyl)-5-nitroimidazole is described.
U.S. Pat. No. 4,822,805, to Takasugi et al., describes pyridylimidazoles as antiinflammatory agents. Specifically, 2-[2-methoxy-4-(methylsulfonyl)phenyl]-4-methyl-5-(3-pyridyl)imidazole is described.
The invention""s imidazolyl compounds are found to show usefulness in vivo as antiinflammatory agents with minimal side effects.
A class of substituted imidazolyl compounds useful in treating inflammation-related disorders is defined by Formula I: 
wherein R1 and R2 are independently selected from aryl, cycloalkyl, cycloalkenyl and heterocyclo, wherein R1 and R2 are optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, haloalkylsulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro;
wherein R3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, cycloalkyloxy, cycloalkyloxyalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocycloalkylcarbonyl, cyanoalkyl, azidoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heterocyclo;
wherein R4 is a radical selected from hydrido, alkyl and fluoro; wherein R5 is selected from hydroxyl and alkoxy; and wherein R6 is hydrido; or wherein R5 and R6 together form a double bond; provided at least one of R1 and R2 is substituted with alkylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable salt thereof.
Compounds of Formula I would be useful for, but not limited to, the treatment of inflammation in a subject, and for treatment of other inflammation-associated disorders, such as, as an analgesic in the treatment of pain and headaches, or as an antipyretic for the treatment of fever. For example, compounds of the invention would be useful to treat arthritis, including but not limited to rheumatoid arthritis, spondyloarthopathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus and juvenile arthritis. Such compounds of the invention would be useful in the treatment of asthma, bronchitis, menstrual cramps, tendinitis, bursitis, and skin-related conditions such as psoriasis, eczema, burns and dermatitis. Compounds of the invention also would be useful to treat gastrointestinal conditions such as inflammatory bowel disease, Crohn""s disease, gastritis, irritable bowel syndrome and ulcerative colitis, and for the prevention or treatment of cancer, such as colorectal cancer. Compounds of the invention would be useful in treating inflammation in such diseases as vascular diseases, migraine headaches, periarteritis nodosa, thyroiditis, aplastic anemia, Hodgkin""s disease, sclerodoma, rheumatic fever, type I diabetes, neuromuscular junction disease including myasthenia gravis, white matter disease including multiple sclerosis, sarcoidosis, nephrotic syndrome, Behcet""s syndrome, polymyositis, gingivitis, nephritis, hypersensitivity, swelling occurring after injury, myocardial ischemia, and the like. The compounds would also be useful in the treatment of ophthalmic diseases such as retinitis, retinopathies, uveitis, conjunctivitis, and of acute injury to the eye tissue. The compounds would also be useful in the treatment of pulmonary inflammation, such as that associated with viral infections and cystic fibrosis. The compounds would also be useful for the treatment of certain central nervous system disorders such as cortical dementias including Alzheimers disease. The compounds of the invention are useful as anti-inflammatory agents, such as for the treatment of arthritis, with the additional benefit of having significantly less harmful side effects. These compounds would also be useful in the treatment of allergic rhinitis, respiratory distress syndrome, endotoxin shock syndrome, atherosclerosis and central nervous system damage resulting from stroke, ischemia and trauma.
Besides being useful for human treatment, these compounds are also useful for veterinary treatment of mammals, including companion animals and farm animals, such as, but not limited to, horses, dogs, cats, cows, sheep and pigs.
The present compounds may also be used in co-therapies, partially or completely, in place of other conventional antiinflammatories, such as together with steroids, NSAIDs, 5-lipoxygenase inhibitors, LTB4 antagonists and LTA4 hydrolase inhibitors.
Suitable LTB4 inhibitors include, among others, ebselen, Bayer Bay-x-1005, Ciba Geigy compound CGS-25019C, Leo Denmark compound ETH-615, Lilly compound LY-293111, Ono compound ONO-4057, Terumo compound TMK-688, Lilly compounds LY-213024, 264086 and 292728, ONO compound ONO-LB457, Searle compound SC-53228, calcitrol, Lilly compounds LY-210073, LY223982, LY233469, and LY255283, ONO compound ONO-LB-448, Searle compounds SC-41930, SC-50605 and SC-51146, and SKandF compound SKF-104493. Preferably, the LTB4 inhibitors are selected from ebselen, Bayer Bay-x-1005, Ciba Geigy compound CGS-25019C, Leo Denmark compound ETH-615, Lilly compound LY-293111, Ono compound ONO-4057, and Terumo compound TMK-688.
Suitable 5-LO inhibitors include, among others, masoprocol, tenidap, zileuton, pranlukast, tepoxalin, rilopirox, flezelastine hydrochloride, enazadrem phosphate, and bunaprolast.
The present invention preferably includes compounds which selectively inhibit cyclooxygenase-2 over cyclooxygenase-1. Preferably, the compounds have a cyclooxygenase-2 IC50 equal to or less than about 0.2 xcexcM, and also have a selectivity ratio of cyclooxygenase-2 inhibition over cyclooxygenase-1 inhibition of at least 50, and more preferably of at least 100. Even more preferably, the compounds have a cyclooxygenase-1 IC50 of greater than about 1.0 xcexcM, and more preferably of greater than 10 xcexcM. such preferred selectivity may indicate an ability to reduce the incidence of common NSAID-induced side effects.
A preferred class of compounds consists of those compounds of Formula I wherein R1 and R2 are independently selected from phenyl, naphthyl, biphenyl, lower cycloalkyl, lower cycloalkenyl and heteroaryl, wherein R1 and R2 are optionally substituted at a substitutable position with one or more radicals independently selected from lower alkylsulfonyl, aminosulfonyl, lower haloalkylsulfonyl, halo, lower alkylthio, lower alkyl, cyano, carboxyl, lower alkoxycarbonyl, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, lower haloalkoxy, amino, lower alkylamino, arylamino and nitro; wherein R3 is a radical selected from hydrido, lower alkyl, lower haloalkyl, lower aralkyl, lower heterocycloalkyl, acyl, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, lower cycloalkyloxy, lower cycloalkyloxyalkyl, lower cycloalkylthio, lower cycloalkylthioalkyl, lower cycloalkylsulfonyl, lower cycloalkylsulfonylalkyl, phenylsulfonyl, lower haloalkylsulfonyl, halo, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylcarbonyl, lower azidoalkyl, lower haloalkylcarbonyl, phenylcarbonyl, lower aralkylcarbonyl, lower heterocycloalkylcarbonyl, lower cyanoalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower N-arylaminoalkyl, lower N-alkyl-N-arylaminoalkyl, lower carboxyalkyl, lower alkoxycarbonylalkyl, lower alkoxycarbonyl, lower alkylthioalkyl, aminocarbonyl, lower alkylaminocarbonyl, lower alkylaminocarbonylalkyl, lower aralkoxy, lower aralkylthio, lower heteroaralkoxy, lower heteroaralkylthio, lower heteroarylalkoxyalkyl, lower heteroarylalkylthioalkyl, lower heteroaryloxyalkyl, lower heteroarylthioalkyl, lower heteroaryloxy, lower heteroarylthio, lower arylthioalkyl, lower aryloxyalkyl, lower arylthio, lower-aryloxy, lower aralkylthioalkyl, lower aralkoxyalkyl, aryl selected from phenyl and naphthyl, and heteroaryl, wherein the aryl and heteroaryl radicals are optionally substituted at a substitutable position with one or more radicals selected from halo, lower alkylthio, lower alkylsulfinyl, lower alkyl, cyano, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl and lower haloalkoxy; wherein R4 is a radical selected from hydrido, lower alkyl and fluoro; and wherein R5 is selected from hydroxyl and lower alkoxy; wherein R6 is hydrido; or wherein R5 and R6 together form a double bond; or a pharmaceutically-acceptable salt thereof.
A class of compounds of particular interest consists of those compounds of Formula I wherein R1 and R2 are independently selected from phenyl, naphthyl, biphenyl, cyclohexyl, cyclohexenyl, benzofuryl, benzodioxolyl, furyl, imidazolyl, thienyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, pyrimidinyl, quinolinyl, isoquinolinyl, benzimidazolyl, pyrazinyl, indolyl, pyrazolyl and pyridyl, wherein R1 and R2 are optionally substituted at a substitutable position with one or more radicals independently selected from methylsulfonyl, aminosulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, fluoro, chloro, bromo, methylthio, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, trifluoromethoxy, amino, methylamino, N,N-dimethylamino, phenylamino and nitro; wherein R3 is a radical selected from hydrido, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, benzyl, phenylethyl, phenylpropyl, furylmethyl, morpholinomethyl, pyrrolidinylmethyl, piperazinylmethyl, piperidinylmethyl, pyridylmethyl, thienylmethyl, formyl, cyano, methoxy, ethoxy, propoxy, n-butoxy, methylthio, ethylthio, isopropylthio, methylsulfonyl, phenylsulfonyl, trifluoromethylsulfonyl, fluoro, chloro, bromo, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, methylthiomethyl, isopropylthiomethyl, cyclohexylthiomethyl, benzyloxy, benzylthio, methylcarbonyl, ethylcarbonyl, phenylcarbonyl, azidomethyl, trifluoromethylcarbonyl, difluoromethylcarbonyl, fluoromethylcarbonyl, benzylcarbonyl, cyanomethyl, cyanobutyl, aminomethyl, methylaminomethyl, N-phenylaminomethyl, N-methyl-N-phenylaminomethyl, acetyl, propanoyl, butanoyl, methoxycarbonylmethyl, ethoxycarbonylethyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, isobutoxycarbonyl, carboxymethyl, carboxypropyl, aminocarbonyl, methylaminocarbonyl, N,N-diethylaminocarbonyl, N-methylaminocarbonylmethyl, pyridyloxy, pyridylthio, phenyloxy, 4-chlorophenoxy, furylmethoxy, furylmethylthio, thienylmethoxy, quinolylmethoxy, pyridylmethoxy, 5-phenylpyridyl-2-methoxy, thienylmethylthio, pyridylmethylthio, benzylthiomethyl, quinolylmethoxymethyl, furylbutoxyethyl, pyridyloxymethyl, pyridylmethoxymethyl, thienyloxyhexyl, thienylthiomethyl, pyridylthiohexyl, furyloxymethyl, furylmethylthiomethyl, quinolylmethylthioethyl, phenylthiomethyl, 2-chlorophenylthiomethyl, 2,6-dichlorophenylthiomethyl, 4-methylphenylthiomethyl, 2-isopropylphenylthiomethyl, 2-methylphenylthiomethyl, phenyloxymethyl, 4-chlorophenyloxymethyl, 4-methylphenyloxymethyl, benzyloxymethyl, 4-methoxybenzyloxymethyl, naphthyl, phenyl, thienyl, furyl, pyridyl, wherein the thienyl, furyl, pyridyl and phenyl radicals are optionally substituted at a substitutable position with one or more radicals selected from fluoro, chloro, bromo, methylthio, methylsulfinyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl and trifluoromethoxy; wherein R4 is a radical selected from hydrido, methyl, ethyl, and fluoro; and wherein R5 is selected from hydroxyl, methoxy, ethoxy, propoxy and n-butoxy; wherein R6 is hydrido; or wherein R5 and R6 together form a double bond; or a pharmaceutically-acceptable salt thereof.
Within Formula I there is a subclass of compounds of high interest represented by Formula II: 
wherein R3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkyloxy, cycloalkyloxyalkyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocycloalkylcarbonyl, cyanoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, aminocarbonyl, azidoalkyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl, wherein the aryl and heteroaryl radicals are optionally substituted at a substitutable position with one or more radicals selected from halo, alkylthio, alkylsulfinyl, alkyl, cyano, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl and haloalkoxy; wherein R7 is a radical selected from alkyl, haloalkyl and amino; and wherein R8 is one or more radicals selected from hydrido, halo, alkyl, haloalkyl, alkoxy, amino, haloalkoxy, cyano, carboxyl, hydroxyl, hydroxyalkyl, alkoxyalkyl, alkylamino, nitro and alkylthio; or a pharmaceutically-acceptable salt thereof.
A preferred class of compounds consists of those compounds of Formula II wherein R3 is a radical selected from hydrido, lower alkyl, lower haloalkyl, lower aralkyl, lower heterocycloalkyl, acyl, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, phenylsulfonyl, lower haloalkylsulfonyl, lower cycloalkyloxy, lower cycloalkyloxyalkyl, lower cycloalkylthio, lower cycloalkylthioalkyl, lower cycloalkylsulfonyl, lower cycloalkylsulfonylalkyl, halo, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylcarbonyl, lower haloalkylcarbonyl, phenylcarbonyl, lower aralkylcarbonyl, lower heterocycloalkylcarbonyl, lower cyanoalkyl, lower azidoalkyl, lower alkylaminoalkyl, lower N-arylaminoalkyl, lower N-alkyl-N-arylaminoalkyl, lower carboxyalkyl, lower alkoxycarbonylalkyl, lower alkoxycarbonyl, lower alkylthioalkyl, aminocarbonyl, lower alkylaminocarbonylalkyl, lower aralkoxy, lower aralkylthio, lower heteroaralkoxy, lower heteroaralkylthio, lower heteroarylalkoxyalkyl, lower heteroarylalkylthioalkyl, lower heteroaryloxyalkyl, lower heteroarylthioalkyl, lower heteroaryloxy, lower heteroarylthio, lower arylthioalkyl, lower aryloxyalkyl, lower arylthio, lower aryloxy, lower aralkylthioalkyl, lower aralkoxyalkyl, aryl selected from phenyl and naphthyl, 5 or 6 membered heteroaryl, wherein the aryl and heteroaryl radicals are optionally substituted at a substitutable position with one or more radicals selected from halo, lower alkylthio, lower alkylsulfinyl, lower alkyl, cyano, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl and lower haloalkoxy; wherein R7 is a radical selected from lower alkyl, lower haloalkyl and amino; and wherein R8 is a radical selected from hydrido, halo, lower alkyl, lower haloalkyl, lower alkoxy, amino, lower haloalkoxy, cyano, carboxyl, hydroxyl, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylamino, nitro and lower alkylthio; or a pharmaceutically-acceptable salt thereof.
A class of compounds of particular interest consists of those compounds of Formula II wherein R3 is a radical selected from hydrido, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, benzyl, phenylethyl, phenylpropyl, furylmethyl, morpholinomethyl, pyrrolidinylmethyl, piperazinylmethyl, piperidinylmethyl, pyridylmethyl, thienylmethyl, formyl, cyano, methoxy, ethoxy, propoxy, n-butoxy, methylthio, ethylthio, isopropylthio, methylsulfonyl, phenylsulfonyl, trifluoromethylsulfonyl, fluoro, chloro, bromo, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, methylthiomethyl, isopropylthiomethyl, cyclohexylthiomethyl, benzyloxy, benzylthio, methylcarbonyl, phenylcarbonyl, trifluoromethylcarbonyl, difluoromethylcarbonyl, fluoromethylcarbonyl, benzylcarbonyl, cyanomethyl, cyanobutyl, azidomethyl, methylaminomethyl, N-phenylaminomethyl, N-methyl-N-phenylaminomethyl, acetyl, propanoyl, butanoyl, methoxycarbonylmethyl, ethoxycarbonylethyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, carboxymethyl, carboxypropyl, aminocarbonyl, N-methylaminocarbonylmethyl, pyridyloxy, pyridylthio, phenyloxy, 4-chlorophenoxy, furylmethoxy, furylmethylthio, thienylmethoxy, quinolylmethoxy, pyridylmethoxy, 5-phenylpyridyl-2-methoxy, thienylmethylthio, pyridylmethylthio, benzylthiomethyl, quinolylmethoxymethyl, furylbutoxyethyl, pyridyloxymethyl, pyridylmethoxymethyl, thienyloxyhexyl, thienylthiomethyl, pyridylthiohexyl, furyloxymethyl, furylmethylthiomethyl, quinolylmethylthioethyl, phenylthiomethyl, 2-chlorophenylthiomethyl, 2,6-dichlorophenylthiomethyl, 4-methylphenylthiomethyl, 2-isopropylphenylthiomethyl, 2-methylphenylthiomethyl, phenyloxymethyl, 4-chlorophenyloxymethyl, 4-methylphenyloxymethyl, benzyloxymethyl, 4-methoxybenzyloxymethyl, naphthyl, phenyl, thienyl, furyl, pyridyl, wherein the thienyl, furyl, pyridyl and phenyl radicals are optionally substituted at a substitutable position with one or more radicals selected from fluoro, chloro, bromo, methylthio, methylsulfinyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl and trifluoromethoxy; wherein R7 is methyl or amino; and wherein R8 is a radical selected from hydrido, methylsulfonyl, fluoro, chloro, bromo, methylthio, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, trifluoromethoxy, amino, methylamino, N,N-dimethylamino, phenylamino and nitro; or a pharmaceutically-acceptable salt thereof.
A family of specific compounds of particular interest within Formula II consists of compounds and pharmaceutically-acceptable salts thereof as follows:
2-(3,4-difluorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole;
2-(4-chlorophenyl)-4-[(4-methylphenoxy)methyl]-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-[(methylthio)methyl)-1H-imidazole;
1,2-bis[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole;
4-[2-(3,4-difluorophenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3-bromo-4-methoxyphenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole-4-carboxaldehyde;
2-(4-chlorophenyl)-4-[[(4-methylphenyl)thiomethyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(3-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl)-4-(trifluoromethyl)-1H-imidazole;
2-(4-chlorophenyl)-4-fluoromethyl)-1-(4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(2-fluorophenyl)-1-[4-(methylsulfonyl)phenyl)-4-(trifluoromethyl)-1H-imidazole;
2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl)-4-(phenylmethoxymethyl)-1H-imidazole;
4-[2-(2-fluorophenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
N,N-dimethyl-4-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]benzenamine;
2-(4-chlorophenyl)-4-[[(1-methylethyl)thio]methyl]-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-[[(cyclohexyl)thio]methyl]-1-[4-(methylsulfonyl)phenyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-[3-(trifluoromethyl)phenyl]-4-(trifluoromethyl)-1H-imidazole;
2-[3-(methoxymethyl)phenyl]-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole;
2-fluoro-N,N-dimethyl-4-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]benzenamine;
2-(3-bromophenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole;
4-[4-(trifluoromethyl)-2-[3-(trifluoromethyl)phenyl]-1H-imidazol-1-yl]benzenesulfonamide;
2-(4-chlorophenyl)-4-[[(2-chlorophenyl)thio]methyl]-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(3-nitrophenyl)-4-(trifluoromethyl)-1H-imidazole;
2-(4-chlorophenyl)-4-[[(2-methylphenyl)thio]methyl]-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
N-methyl-4-[1-[4-(methylsulfonyl)phenyl)-4-(trifluoromethyl)-1H-imidazol-2-yl]benzenamine;
3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]benzenamine;
N,N-dimethyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]benzenamine;
N-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]benzenamine;
2-fluoro-N-methyl-4-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]benzenamine;
2-(4-chlorophenyl)-4-[[(2,6-dichlorophenyl)thio]methyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-[[(2-(1-methylethyl)phenyl]thio]methyl]-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-[2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl)-1H-imidazol-4-yl]ethanone;
1-[4-(methylsulfonyl)phenyl]-2-[3-(methylthio)phenyl]-4-(trifluoromethyl)-1H-imidazole;
4-[2-(3-bromophenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
2-(3-chloro-5-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole;
4-[2-(3-chloro-5-methylphenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole-4-acetonitrile;
2-(3-fluoro-5-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole;
2-(3-fluoro-5-methoxyphenyl)-1-(4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole;
4-[2-(3-fluoro-5-methylphenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole-4-acetic acid;
4-[2-(3-fluoro-5-methoxyphenyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
2-(4-chlorophenyl)-4-trifluoromethyl-1-(4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-difluoromethyl-1-(4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-methyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-ethyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-phenyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(4-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(4-bromophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(2-naphthyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-[4-(trifluoromethoxy)phenyl]-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(3-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(3-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-phenoxymethyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(4-chlorophenoxy)methyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(4-fluorophenoxy)methyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-phenylthiomethyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(N-phenyl-N-methylamino)methyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(2-quinolyl)methoxymethyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-methoxymethyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(4-methoxybenzyloxy)methyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole-4-methanol;
2-(4-chlorophenyl)-4-formyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole-4-carbonitrile;
2-(4-chlorophenyl)-4-benzyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-phenylethyl-1-(4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-hexyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-hexylcarbonyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-phenylcarbonyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-benzylcarbonyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(1-hydroxy-1-phenyl-methyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(1-hexanol)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-1-[(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-octyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-methoxy-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-butoxy-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-methylthio-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethylsulfonyl-1H-imidazole;
2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethylcarbonyl-1H-imidazole;
2-(4-chlorophenyl)-4-(2-thienyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(3-furyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-(4-pyridyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-chloro-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
2-(4-chlorophenyl)-4-fluoro-1-[4-(methylsulfonyl)phenyl]-1H-imidazole;
methyl [2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl]carboxylate;
[2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl]carboxamide;
methyl [2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl)carboxamide;
4-[2-(4-chlorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-difluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-methyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-ethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-fluorophenyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-bromophenyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-chlorophenyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(2-naphthyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-[4-(trifluoromethoxy)phenyl]-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(3-chlorophenyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(3-fluorophenyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-methoxyphenyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenoxymethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-chlorophenoxy)methyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-fluorophenoxy)methyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenylthiomethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(N-phenyl-N-methylamino)methyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(2-quinolyl)methoxymethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-methoxymethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-methoxybenzyloxy)methyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-hydroxymethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-formyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-cyano-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-benzyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenylethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-hexyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-hexylcarbonyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenylcarbonyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-benzylcarbonyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(1-hydroxy-1-phenyl-methyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(1-hexanol)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-octyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-methoxy-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-butoxy-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-methylthio-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(2-thienyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(3-furyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-pyridyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-chloro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-fluoro-1H-imidazol-1-yl]benzenesulfonamide;
[2-(4-chlorophenyl)-1-[4-(aminosulfonyl)phenyl)-1H-imidazol-4-yl]carboxylic acid;
methyl[2-(4-chlorophenyl)-1-[4-(aminosulfonyl)phenyl)-1H-imidazol-4-yl]carboxylate;
[2-(4-chlorophenyl)-1-[4-(aminosulfonyl)phenyl)-1H-imidazol-4-yl]carboxamide;
methyl[2-(4-chlorophenyl)-1-[4-(aminosulfonyl)phenyl)-1H-imidazol-4-yl]carboxamide;
2-(3-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(2-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(4-fluoro-3-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(4-chloro-3-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(4-fluoro-3-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(4-chloro-3-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(3-fluoro-4-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(3-chloro-4-methylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(3-fluoro-4-methylthiophenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(3-chloro-4-methylthiophenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(4-fluoro-3-methylthiophenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(4-chloro-3-methylthiophenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(3,5-dimethyl-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(3,5-dichloro-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(3,5-difluoro-4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(3,4-dimethylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-(3,5-dichlorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
4-[2-(3-methylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(2-methylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-fluoro-3-methylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chloro-3-methylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-fluoro-3-methoxyphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chloro-3-methoxyphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3-fluoro-4-methylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3-chloro-4-methylthiophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3-fluoro-4-methylthiophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-fluoro-3-methylthiophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chloro-4-methylthiophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,5-dimethyl-4-methoxyphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,5-dichloro-4-methoxyphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,5-difluoro-4-methoxyphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,4-dimethylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,5-dichlorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
ethyl [2-(4-chlorophenyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-4-yl]carboxylate;
ethyl [1-[4-(aminosulfonyl)phenyl]-2-(4-chlorophenyl)-1H-imidazol-4-yl]carboxylate;
1-[4-(methylsulfonyl)phenyl]-2-(4-methylphenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(3-chlorophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methyl-3-chlorophenyl)-4-trifluoromethyl-1H-imidazole;
5-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]-1,3-benzodioxole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methoxyphenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(3-fluorophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-fluorophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methoxy-3-fluorophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-phenyl-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methoxy-3-chlorophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-[4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-bromophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(2-chlorophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-ethylphenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-butylphenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-[4-(difluoromethyl)phenyl]-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-butoxyphenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-[4-(methylthio)phenyl]-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methoxy-3,5-dichloro-phenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methyl-3,5-difluorophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(2,4-dichlorophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(3,4-dichlorophenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-[4-(trifluoromethyl)phenyl]-4-trifluoromethoxy-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(3,5-dimethyl-4-methoxy-phenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(3,4-dimethylphenyl)-4-trifluoromethyl-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-aminophenyl)-4-trifluoromethyl-1H-imidazole;
4-[2-(4-methylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3-chlorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methyl-3-chlorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
5-[1-[4-(aminosulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]-1,3-benzodioxole;
4-[2-(4-methoxyphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-(2-(3-fluorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-fluorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methoxy-3-fluorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-phenyl-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methoxy-3-chlorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-[4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-bromophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(2-chlorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-ethylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-butylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-[4-(difluoromethyl)phenyl]-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-butoxyphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-[4-(methylthio)phenyl]-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methoxy-3,5-dichloro-phenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methyl-3,5-difluorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(2,4-dichlorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,4-dichlorophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-[4-(trifluoromethoxy)phenyl]-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,5-dimethyl-4-methoxy-phenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,4-dimethylphenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide; and
4-[2-(4-aminophenyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide.
Within Formula I there is a second subclass of compounds of high interest represented by Formula III: 
wherein R3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, cycloalkyloxy, cycloalkyloxyalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocycloalkylcarbonyl, cyanoalkyl, azidoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, aminocarbonyl, N-alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein the aryl and heteroaryl radicals are optionally substituted at a substitutable position with one or more radicals selected from halo, alkylthio, alkylsulfinyl, alkyl, cyano, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl and haloalkoxy; wherein R4 is a radical selected from hydrido, alkyl and fluoro; wherein R9 is one or more radicals selected from hydrido, halo, alkyl, haloalkyl, alkoxy, amino, haloalkoxy, cyano, carboxyl, hydroxyl, hydroxyalkyl, alkoxyalkyl, alkylamino, nitro and alkylthio; and wherein R10 is a radical selected from alkyl, haloalkyl and amino; or a pharmaceutically-acceptable salt thereof.
A preferred class of compounds consists of those compounds of Formula III wherein R3 is a radical selected from hydrido, lower alkyl, lower haloalkyl, lower aralkyl, lower heterocycloalkyl, lower heteroaralkyl, acyl, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, phenylsulfonyl, lower haloalkylsulfonyl, halo, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylcarbonyl, lower haloalkylcarbonyl, phenylcarbonyl, lower aralkylcarbonyl, lower cyanoalkyl, lower azidoalkyl, lower alkylaminoalkyl, lower N-arylaminoalkyl, lower N-alkyl-N-arylaminoalkyl, lower carboxyalkyl, lower alkoxycarbonylalkyl, lower alkoxycarbonyl, lower alkylthioalkyl, aminocarbonyl, lower alkylaminocarbonylalkyl, lower aralkoxy, lower aralkylthio, lower heteroaralkoxy, lower heteroaralkylthio, lower heteroarylalkoxyalkyl, lower heteroarylalkylthioalkyl, lower heteroaryloxyalkyl, lower heteroarylthioalkyl, lower heteroaryloxy, lower heteroarylthio, lower arylthioalkyl, lower aryloxyalkyl, lower arylthio, lower aryloxy, lower aralkylthioalkyl, lower aralkoxyalkyl, aryl selected from phenyl and naphthyl, 5 or 6 membered heteroaryl, wherein the aryl and heteroaryl radicals are optionally substituted at a substitutable position with one or more radicals selected from halo, lower alkylthio, lower alkylsulfinyl, lower alkyl, cyano, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl and lower haloalkoxy; wherein R4 is a radical selected from hydrido, lower alkyl and fluoro; wherein R9 is a radical selected from hydrido, halo, lower alkyl, lower haloalkyl, lower alkoxy, amino, lower haloalkoxy, cyano, carboxyl, hydroxyl, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylamino, nitro and lower alkylthio; and wherein R10 is a radical selected from lower alkyl, lower haloalkyl and amino; or a pharmaceutically-acceptable salt thereof.
A class of compounds of particular interest consists of those compounds of Formula III wherein R3 is a radical selected from hydrido, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, benzyl, phenylethyl, phenylpropyl, furylmethyl, morpholinomethyl, pyrrolidinylmethyl, piperazinylmethyl, piperidinylmethyl, pyridylmethyl, thienylmethyl, formyl, cyano, methoxy, ethoxy, propoxy, n-butoxy, methylthio, ethylthio, methylsulfonyl, phenylsulfonyl, trifluoromethylsulfonyl, fluoro, chloro, bromo, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, methylthiomethyl, benzyloxy, benzylthio, methylcarbonyl, phenylcarbonyl, trifluoromethylcarbonyl, difluoromethylcarbonyl, fluoromethylcarbonyl, benzylcarbonyl, cyanomethyl, cyanobutyl, azidomethyl, methylaminomethyl, N-phenylaminomethyl, N-methyl-N-phenylaminomethyl, acetyl, propanoyl, butanoyl, methoxycarbonylmethyl, ethoxycarbonylethyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, aminocarbonyl, methylaminocarbonylmethyl, pyridyloxy, pyridylthio, phenyloxy, 4-chlorophenoxy, furylmethoxy, furylmethylthio, thienylmethoxy, quinolylmethoxy, pyridylmethoxy, 5-phenylpyridyl-2-methoxy, thienylmethylthio, pyridylmethylthio, quinolylmethoxymethyl, furylbutoxyethyl, pyridyloxymethyl, pyridylmethoxymethyl, thienyloxyhexyl, thienylthiomethyl, pyridylthiohexyl, furyloxymethyl, furylmethylthiomethyl, quinolylmethylthioethyl, phenylthiomethyl, phenyloxymethyl, 4-chlorophenyloxymethyl, benzyloxymethyl, 4-methoxybenzyloxymethyl, naphthyl, phenyl, thienyl, furyl, pyridyl, wherein the thienyl, furyl, pyridyl and phenyl radicals are optionally substituted at a substitutable position with one or more radicals selected from fluoro, chloro, bromo, methylthio, methylsulfinyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl and trifluoromethoxy; wherein R4 is a radical selected from hydrido, methyl, ethyl and fluoro; wherein R9 is a radical selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, isopropyl, tert-butyl, isobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, methoxy, ethoxy, isopropoxy, tert-butoxy, propoxy, butoxy, isobutoxy, pentoxy, methylenedioxy, amino, trifluoromethoxy, cyano, carboxyl, hydroxyl, nitro, hydroxymethyl, methoxymethyl, ethoxymethyl, methylamino, methylthio, ethylthio, propylthio and butylthio; and wherein R10 is methyl, fluoromethyl or amino, or a pharmaceutically-acceptable salt thereof.
A family of specific compounds of particular interest within Formula III consists of compounds and pharmaceutically-acceptable salts thereof as follows:
1-(4-chlorophenyl)-4-trifluoromethyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-difluoromethyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-methyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-ethyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-phenyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(4-fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(4-bromophenyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(2-naphthyl)-2-[4-(methylsulfonyl)phenyl)-1H-imidazole;
1-(4-chlorophenyl)-4-[4-(trifluoromethoxy)phenyl]-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(3-chlorophenyl)-2-[4-(methylsulfonyl)phenyl)-1H-imidazole;
1-(4-chlorophenyl)-4-(3-fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(4-methoxyphenyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-phenoxymethyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(4-chlorophenoxy)methyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(4-fluorophenoxy)methyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-phenylthiomethyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(N-phenyl-N-methylamino)methyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(2-quinolyl)methoxymethyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-methoxymethyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(4-methoxybenzyloxy)methyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-hydroxymethyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-formyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-cyano-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-benzyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-phenylethyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-hexyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-hexylcarbonyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-phenylcarbonyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-benzylcarbonyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(1-hydroxy-2-phenyl-methyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(1-hexanol)-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-2-[(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-octyl-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-methoxy-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-butoxy-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-methylthio-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(2-thienyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(3-furyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-(4-pyridyl)-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-chloro-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
1-(4-chlorophenyl)-4-fluoro-2-[4-(methylsulfonyl)phenyl]-1H-imidazole;
[1-(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl)-1H-imidazol-4-yl]carboxylic acid;
methyl[1-(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl)-1H-imidazol-4-yl]carboxylate;
[1-(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl)-1H-imidazol-4-yl]carboxamide;
methyl[1-(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl)-1H-imidazol-4-yl]carboxamide;
4-[1-(4-chlorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-difluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-methyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-ethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-fluorophenyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-bromophenyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-chlorophenyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(2-naphthyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-[4-(trifluoromethoxy)phenyl]-1H-imidazol-2-yl]benzenesulfonamide;
4-(1-(4-chlorophenyl)-4-(3-chlorophenyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(3-fluorophenyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-methoxyphenyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenoxymethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-chlorophenoxy)methyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-fluorophenoxy)methyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenylthiomethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(N-phenyl-N-methylamino)methyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(2-quinolyl)methoxymethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-methoxymethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-4-methoxybenzyloxy)methyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-hydroxymethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-formyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-cyano-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-benzyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenylethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-hexyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-hexylcarbonyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenylcarbonyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-benzylcarbonyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(1-hydroxy-2-phenyl-methyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(1-hexanol)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-octyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-methoxy-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-butoxy-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-methylthio-1H-imidazol-2-yl]benzenesulfonamide,
4-[1-(4-chlorophenyl)-4-(3-thienyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(2-furyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(3-pyridyl)-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-chloro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-fluoro-1H-imidazol-2-yl]benzenesulfonamide;
[1-(4-chlorophenyl)-2-[4-(aminosulfonyl)phenyl)-1H-imidazol-4-yl]carboxylic acid;
methyl[1-(4-chlorophenyl)-2-[4-(aminosulfonyl)phenyl)-1H-imidazol-4-yl]carboxylate;
[1-(4-chlorophenyl)-2-[4-(aminosulfonyl)phenyl)-1H-imidazol-4-yl]carboxamide;
methyl[1-(4-chlorophenyl)-2-[4-(aminosulfonyl)phenyl)-1H-imidazol-4-yl]carboxamide;
2-[4-(methylsulfonyl)phenyl]-1-(4-methylphenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3-chlorophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-2-(4-methyl-3-chlorophenyl)-4-trifluoromethyl-1H-imidazole;
5-[2-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-1-yl]-1,3-benzodioxole;
2-[4-(methylsulfonyl)phenyl]-2-(4-methoxyphenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3-fluorophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-fluorophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-methoxy-3-fluorophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-phenyl-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-methoxy-3-chlorophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-[4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-bromophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(2-chlorophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-ethylphenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-butylphenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-[4-(difluoromethyl)phenyl]-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-butoxyphenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-[4-(methylthio)phenyl]-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-methoxy-3,5-dichloro-phenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl)-1-(4-methyl-3,5-difluorophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(2,4-dichlorophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3,4-dichlorophenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-[4-(trifluoromethyl)phenyl]-4-trifluoromethoxy-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3,5-dimethyl-4-methoxy-phenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3,4-dimethylphenyl)-4-trifluoromethyl-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-aminophenyl)-4-trifluoromethyl-1H-imidazole;
4-[1-(4-methylphenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(3-chlorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-methyl-3-chlorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
5-[2-[4-(aminosulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-1-yl]-1,3-benzodioxole;
4-[1-(3-fluorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-fluorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-methoxy-3-fluorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-phenyl-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-methoxy-3-chlorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-(trifluoromethyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-bromophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(2-chlorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-ethylphenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-butylphenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-[4-(difluoromethyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-butoxyphenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-[4-(methylthio)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-methoxy-3,5-dichloro-phenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-methyl-3,5-difluorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(2,4-dichlorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(3,4-dichlorophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-(trifluoromethoxy)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(3,5-dimethyl-4-methoxy-phenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(3,4-dimethylphenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide; and
4-[1-(4-aminophenyl)-4-trifluoromethyl-1H-imidazol-2-yl]benzenesulfonamide.
Within Formula I there is a third subclass of compounds of high interest represented by Formula IV: 
wherein R3 is selected from alkyl, haloalkyl, alkylsulfonylalkyl, cycloalkylthioalkyl, alkoxycarbonyl, aralkoxyalkyl, aryloxyalkyl, arylthioalkyl, N-aryl-N-alkylaminoalkyl, heteroarylalkoxyalkyl, heterocyclocarbonyl, heteroaryloxyalkyl, N-alkoxy-N-alkylaminocarbonyl, heteroaralkylthioalkyl, heteroarylthioalkyl and aryl optionally substituted at a substitutable position with halo, alkoxy and haloalkoxy; and wherein R11 and R12 are independently selected from hydrido, halo, alkyl, haloalkyl, alkoxy, alkylsulfonyl, haloalkylsulfonyl and sulfamyl; or a pharmaceutically-acceptable salt thereof.
A preferred class of compounds consists of those compounds of Formula IV wherein R3 is selected from lower alkyl, lower haloalkyl, lower aralkoxyalkyl, lower aryloxyalkyl, lower alkoxycarbonyl, lower arylthioalkyl, lower heteroaralkylthioalkyl, lower heteroarylthioalkyl, lower N-aryl-N-alkylaminoalkyl, lower heteroarylalkoxyalkyl and aryl selected from naphthyl, phenyl and biphenyl, wherein the aryl radical is optionally substituted at a substitutable position with halo, lower alkoxy and lower haloalkoxy; and wherein R11 and R12 are independently selected from hydrido, halo, lower alkyl, lower haloalkyl, lower alkoxy, lower alkylsulfonyl, lower haloalkylsulfonyl and sulfamyl; or a pharmaceutically-acceptable salt thereof.
A class of compounds of particular interest consists of those compounds of Formula IV wherein R3 is selected from methyl, ethyl, isopropyl, tert-butyl, isobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, ethoxycarbonyl, methoxycarbonyl, benzyloxymethyl, phenylthiomethyl, pyridylthiomethyl, pyridylmethylthiomethyl, phenyloxymethyl, 4-chlorophenyloxymethyl, N-phenyl-N-methylaminomethyl, quinolyloxymethyl and aryl selected from naphthyl and phenyl, wherein the aryl radical is optionally substituted at a substitutable position with fluoro, chloro, bromo, iodo, methoxy, ethoxy, isopropoxy, tert-butoxy, propoxy, butoxy, isobutoxy, pentoxy, methylenedioxy and trifluoromethoxy; and wherein R11 and R12 are independently selected from hydrido, fluoro, chloro, bromo, iodo, methyl, ethyl, isopropyl, tert-butyl, isobutyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, methoxy, ethoxy, isopropoxy, tert-butoxy, propoxy, butoxy, isobutoxy, pentoxy, methylenedioxy, methylsulfonyl, fluoromethylsulfonyl and sulfamyl; or a pharmaceutically-acceptable salt thereof.
A family of specific compounds of particular interest within Formula IV consists of compounds and pharmaceutically-acceptable salts thereof as follows:
2-[4-(dimethylamino)-3-fluorophenyl]-4,5-dihydro-4-hydroxy-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole;
2-(4-chlorophenyl)-4-trifluoromethyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-difluoromethyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-methyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-ethyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-phenyl-1-[4-(methylsulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(4-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(4-bromophenyl)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(2-naphthyl)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-[4-(trifluoromethoxy)phenyl]-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(3-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(3-chlorophenyl)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(4-methoxyphenyl)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-phenoxymethyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(4-chlorophenoxy)methyl-1-(4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(4-fluorophenoxy)methyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-phenylthiomethyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(N-phenyl-N-methylamino)methyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4 chlorophenyl)-4-(2-quinolyl)methoxymethyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-methoxymethyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(4-methoxybenzyloxy)methyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-hydroxymethyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-formyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-cyano-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-benzyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-phenylethyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-hexyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-hexylcarbonyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-phenylcarbonyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-benzylcarbonyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(1-hydroxy-1-phenyl-methyl)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(1-hexanol)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-1-[(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-octyl-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-methoxy-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-butoxy-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-methylthio-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(2-thienyl)-1-4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-(2-furyl)-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-1-(4-(methylsulfonyl)phenyl]-4-(4-pyridyl)-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-chloro-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-chlorophenyl)-4-fluoro-1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
[2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxylic acid;
methyl[2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxylate;
[2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxamide;
methyl[2-(4-chlorophenyl)-1-[4-(methylsulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxamide;
4-[2-(4-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-difluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-methyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-ethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-fluorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-bromophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-chlorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(2-naphthyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-(trifluoromethoxy)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(3-chlorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(3-fluorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-methoxyphenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenoxymethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-chlorophenoxy)methyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-fluorophenoxy)methyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenylthiomethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(N-phenyl-N-methylamino)methyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(2-quinolyl)methoxymethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-methoxymethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-methoxybenzyloxy)methyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-hydroxymethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-formyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-cyano-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-benzyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenylethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-hexyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-hexylcarbonyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-phenylcarbonyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-benzylcarbonyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(1-hydroxy-1-phenyl-methyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(1-hexanol)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-octyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-methoxy-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-butoxy-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-methylthio-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(3-thienyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(2-furyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-(4-pyridyl)-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-chloro-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-chlorophenyl)-4-fluoro-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
[2-(4-chlorophenyl)-1-[4-(aminosulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxylic acid;
methyl[2-(4-chlorophenyl)-1-[4-(aminosulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxylate;
[2-(4-chlorophenyl)-1-[4-(aminosulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxamide;
methyl[2-(4-chlorophenyl)-1-[4-(aminosulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxamide;
2-[4-(methylsulfonyl)phenyl]-1-(4-methylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methyl-3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
5-[1-[4-(methylsulfonyl)phenyl]-4-hydroxy-4-trifluoromethyl-4,5-dihydro-1H-imidazol-2-yl]-1,3-benzodioxole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methoxyphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(3-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methoxy-3-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-phenyl-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methoxy-3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-[4-(trifluoromethyl)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-bromophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-ethylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-butylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-[4-(difluoromethyl)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-butoxyphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-[4-(methylthio)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methoxy-3,5-dichloro-phenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(4-methyl-3,5-difluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(2,4-dichlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-(3,4-dichlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-[4-(methylsulfonyl)phenyl]-2-[4-(trifluoromethyl)phenyl]-4-trifluoromethoxy-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(3,5-dimethyl-4-methoxy-phenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(3,4-dimethylphenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-(4-aminophenyl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
4-[2-(4-methylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methyl-3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
5-[1-[4-(aminosulfonyl)phenyl]-4-hydroxy-4-trifluoromethyl-4,5-dihydro-1H-imidazol-2-yl]-1,3-benzodioxole;
4-[2-(4-methoxyphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methoxy-3-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-phenyl-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methoxy-3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-[4-(trifluoromethyl)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-bromophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(2-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-ethylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-butylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-[4-(difluoromethyl)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-butoxyphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-[4-(methylthio)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methoxy-3,5-dichloro-phenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methyl-3,5-difluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(2,4-dichlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,4-dichlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-[4-(trifluoromethoxy)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,5-dimethyl-4-methoxy-phenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3,4-dimethylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-aminophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-1-yl]benzenesulfonamide;
1-(4-chlorophenyl)-4-trifluoromethyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-difluoromethyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-methyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-ethyl-2-(4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-phenyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(4-fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
4-(4-bromophenyl)-1-(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(3-chlorophenyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(3-fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(4-methoxyphenyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1,4-bis(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(2-naphthyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-[4-(trifluoromethoxy)phenyl]-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-phenoxymethyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(4-chlorophenoxy)methyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(4-fluorophenoxy)methyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-phenylthiomethyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(N-phenyl-N-methylamino)methyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(2-quinolyl)methoxymethyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-methoxymethyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(4-methoxybenzyloxy)methyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-hydroxymethyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-formyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-cyano-2-[4-(methylsulfonyl)phenyl-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-benzyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-phenylethyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-hexyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-hexylcarbonyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-phenylcarbonyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-benzylcarbonyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(1-hydroxy-2-phenyl-methyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(1-hexanol)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-2-[(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-octyl-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-methoxy-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-butoxy-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-methylthio-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(2-thienyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(2-furyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-(4-pyridyl)-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-chloro-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
1-(4-chlorophenyl)-4-fluoro-2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazole;
[1-(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxylic acid;
methyl[1-(4-chlorophenyl)-2-[4-(methylsulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxylate;
[1-(4-chlorophenyl)-2-(4-(methylsulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxamide;
methyl[1-(4-chlorophenyl)-2-(4-(methylsulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxamide;
4-[1-(4-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-difluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-methyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-ethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-fluorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-bromophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-chlorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(2-naphthyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-[4-(trifluoromethoxy)phenyl]-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(3-chlorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(3-fluorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-methoxyphenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenoxymethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-chlorophenoxy)methyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-fluorophenoxy)methyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenylthiomethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(N-phenyl-N-methylamino)methyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(2-quinolyl)methoxymethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-methoxymethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(4-methoxybenzyloxy)methyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-hydroxymethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-formyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-cyano-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-benzyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenylethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-hexyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-hexylcarbonyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-phenylcarbonyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-benzylcarbonyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(1-hydroxy-2-phenyl-methyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(1-hexanol)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-octyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-methoxy-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-butoxy-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-methylthio-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(2-thienyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(2-furyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-(3-pyridyl)-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-chloro-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-chlorophenyl)-4-fluoro-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
[1-(4-chlorophenyl)-2-[4-(aminosulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxylic acid;
methyl[1-(4-chlorophenyl)-2-[4-(aminosulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxylate;
[1-(4-chlorophenyl)-2-[4-(aminosulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxamide;
methyl[1-(4-chlorophenyl)-2-[4-(aminosulfonyl)phenyl)-4-hydroxy-4,5-dihydro-1H-imidazol-4-yl]carboxamide;
2-[4-(methylsulfonyl)phenyl]-1-(4-methylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-methyl-3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
5-[2-[4-(methylsulfonyl)phenyl]-4-hydroxy-4-trifluoromethyl-4,5-dihydro-1H-imidazol-1-yl]-1,3-benzodioxole;
2-[4-(methylsulfonyl)phenyl]-1-(4-methoxyphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-methoxy-3-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-phenyl-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-methoxy-3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-[4-(trifluoromethyl)phenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-bromophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(1-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-ethylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-butylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-[4-(difluoromethyl)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-butoxyphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-[4-(methylthio)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-4-(methylsulfonyl)phenyl]-1-(4-methoxy-3,5-dichloro-phenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-methyl-3,5-difluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(2,4-dichlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3,4-dichlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-[4-(trifluoromethyl)phenyl]-4-trifluoromethoxy-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3,5-dimethyl-4-methoxy-phenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(3,4-dimethylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
2-[4-(methylsulfonyl)phenyl]-1-(4-aminophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazole;
4-[1-(4-methylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-4-methyl-3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
5-[2-[4-(aminosulfonyl)phenyl]-4-hydroxy-4,5-dihydro-4-trifluoromethyl-1H-imidazol-1-yl]-1,3-benzodioxole;
4-[1-(3-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-methoxy-3-fluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-phenyl-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-methoxy-3-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-[4-(trifluoromethyl)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-bromophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(1-chlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-ethylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-butylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-[4-(difluoromethyl)phenyl-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-butoxyphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-[4-(methylthio)phenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-methoxy-3,5-dichloro-phenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(4-methyl-3,5-difluorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(2,4-dichlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(3,4-dichlorophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-[4-(trifluoromethoxy)phenyl]-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(3,5-dimethyl-4-methoxy-phenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide;
4-[1-(3,4-dimethylphenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide; and
4-[1-(4-aminophenyl)-4-trifluoromethyl-4-hydroxy-4,5-dihydro-1H-imidazol-2-yl]benzenesulfonamide.
Within Formula I there is a fourth subclass of compounds of high interest represented by Formula V: 
wherein R3 is a radical selected from hydrido, alkyl, haloalkyl, aralkyl, heterocycloalkyl, heteroaralkyl, acyl, cyano, alkoxy, alkylthio, alkylthioalkyl, alkylsulfonyl, cycloalkylthio, cycloalkylthioalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl, haloalkylsulfonyl, arylsulfonyl, halo, hydroxyalkyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, heterocyclocarbonyl, cyanoalkyl, aminoalkyl, alkylaminoalkyl, N-arylaminoalkyl, N-alkyl-N-arylaminoalkyl, carboxyalkyl, alkoxycarbonylalkyl, alkoxycarbonyl, haloalkylcarbonyl, carboxyl, aminocarbonyl, alkylaminocarbonyl, alkylaminocarbonylalkyl, heteroarylalkoxyalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, aralkoxy, aralkylthio, heteroaralkoxy, heteroaralkylthio, heteroarylalkylthioalkyl, heteroaryloxy, heteroarylthio, arylthioalkyl, aryloxyalkyl, arylthio, aryloxy, aralkylthioalkyl, aralkoxyalkyl, aryl and heteroaryl; wherein R4 is a radical selected from hydrido, alkyl and halo; and wherein R13 and R14 are independently selected from aryl and heterocyclo, wherein R13 and R14 are optionally substituted at a substitutable position with one or more radicals independently selected from alkylsulfonyl, aminosulfonyl, halo, alkylthio, alkyl, cyano, carboxyl, alkoxycarbonyl, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, haloalkoxy, amino, alkylamino, arylamino and nitro; provided at least one of R13 and R14 is aryl substituted with alkylsulfonyl or aminosulfonyl; or a pharmaceutically-acceptable salt thereof.
A preferred class of compounds consists of those compounds of Formula V wherein R3 is a radical selected from hydrido, lower alkyl, lower haloalkyl, lower aralkyl, lower heterocycloalkyl, lower heteroaralkyl, acyl, cyano, lower alkoxy, lower alkylthio, lower alkylsulfonyl, phenylsulfonyl, lower haloalkylsulfonyl, halo, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylcarbonyl, lower haloalkylcarbonyl, phenylcarbonyl, lower aralkylcarbonyl, lower cyanoalkyl, lower aminoalkyl, lower alkylaminoalkyl, lower N-arylaminoalkyl, lower N-alkyl-N-arylaminoalkyl, lower carboxyalkyl, lower alkoxycarbonylalkyl, lower alkoxycarbonyl, carboxyl, lower alkylthioalkyl, aminocarbonyl, lower alkylaminocarbonyl, lower alkylaminocarbonylalkyl, lower aralkoxy, lower aralkylthio, lower heteroaralkoxy, lower heteroaralkylthio, lower heteroarylalkoxyalkyl, lower heteroarylalkylthioalkyl, lower heteroaryloxyalkyl, lower heteroarylthioalkyl, lower heteroaryloxy, lower heteroarylthio, lower arylthioalkyl, lower aryloxyalkyl, lower arylthio, lower aryloxy, lower aralkylthioalkyl, lower aralkoxyalkyl, aryl selected from phenyl and naphthyl, 5 or 6 membered heteroaryl, wherein the aryl and heteroaryl radicals are optionally substituted at a substitutable position with one or more radicals selected from halo, lower alkylthio, lower alkylsulfinyl, lower alkyl, cyano, lower haloalkyl, hydroxyl, lower alkoxy, lower hydroxyalkyl and lower haloalkoxy; wherein R4 is a radical selected from hydrido, lower alkyl and halo; and wherein R13 and R14 are independently selected from phenyl and heteroaryl, wherein R13 and R14 are optionally substituted at a substitutable position with one or more radicals independently selected from lower methylsulfonyl, aminosulfonyl, lower alkylthio, lower alkyl, lower haloalkyl, lower alkoxy, lower hydroxyalkyl, lower alkoxyalkyl, and lower haloalkoxy; or a pharmaceutically-acceptable salt thereof.
A class of compounds of particular interest consists of those compounds of Formula V wherein R3 is a radical selected from hydrido, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, benzyl, phenylethyl, phenylpropyl, furylmethyl, morpholinomethyl, pyrrolidinylmethyl, piperazinylmethyl, piperidinylmethyl, pyridylmethyl, thienylmethyl, formyl, cyano, methoxy, ethoxy, propoxy, n-butoxy, methylthio, ethylthio, isopropylthio, methylsulfonyl, phenylsulfonyl, trifluoromethylsulfonyl, fluoro, chloro, bromo, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, methylthiomethyl, isopropylthiomethyl, cyclohexylthiomethyl, benzyloxy, benzylthio, methylcarbonyl, ethylcarbonyl, phenylcarbonyl, trifluoromethylcarbonyl, difluoromethylcarbonyl, fluoromethylcarbonyl, benzylcarbonyl, pyrrolidinylcarbonyl, cyanomethyl, cyanobutyl, aminomethyl, methylaminomethyl, N-phenylaminomethyl, N-methyl-N-phenylaminomethyl, acetyl, propanoyl, butanoyl, methoxycarbonylmethyl, ethoxycarbonylethyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, carboxyl, carboxymethyl, carboxypropyl, aminocarbonyl, methylaminocarbonyl, N,N-diethylaminocarbonyl, N-methoxy-N-methylaminocarbonyl, methylaminocarbonylmethyl, pyridyloxy, pyridylthio, phenyloxy, 4-chlorophenoxy, furylmethoxy, furylmethylthio, thienylmethoxy, quinolylmethoxy, pyridylmethoxy, 5-phenylpyridyl-2-methoxy, thienylmethylthio, pyridylmethylthio, quinolylmethoxymethyl, furylbutoxyethyl, pyridyloxymethyl, pyridylmethoxymethyl, thienyloxyhexyl, thienylthiomethyl, pyridylthiohexyl, furyloxymethyl, furylmethylthiomethyl, quinolylmethylthioethyl, phenylthiomethyl, 2-chlorophenylthiomethyl, 2,6-dichlorophenylthiomethyl, 4-methylphenylthiomethyl, 2-isopropylphenylthiomethyl, 2-methylphenylthiomethyl, phenyloxymethyl, 4-chlorophenyloxymethyl, 4-methylphenyloxymethyl, benzyloxymethyl, 4-methoxybenzyloxymethyl, naphthyl, phenyl, thienyl, furyl, pyridyl, wherein the thienyl, furyl, pyridyl and phenyl radicals are optionally substituted at a substitutable position with one or more radicals selected from fluoro, chloro, bromo, methylthio, methylsulfinyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl and trifluoromethoxy; wherein R4 is a radical selected from hydrido, methyl, ethyl, fluoro, chloro and bromo; and wherein R13 and R14 are independently selected from phenyl, imidazolyl, thienyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, pyrazinyl, pyrimidinyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, pyrazolyl and pyridyl, wherein R13 and R14 are optionally substituted at a substitutable position with one or more radicals independently selected from methylsulfonyl, aminosulfonyl, fluoromethylsulfonyl, difluoromethylsulfonyl, fluoro, chloro, bromo, methylthio, methylsulfinyl, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, cyano, carboxyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, pentoxycarbonyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, hydroxyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, trifluoromethoxy, amino, methylamino, N,N-diethylamino, phenylamino and nitro; or a pharmaceutically-acceptable salt thereof.
A class of compounds of even more particular interest consists of those compounds of Formula V wherein R3 is a radical selected from hydrido, cyano, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl and 2-methylphenylthiomethyl; wherein R4 is hydrido; wherein R13 is phenyl substituted with methylsulfonyl or aminosulfonyl; and wherein R14 is selected from imidazolyl, thienyl, thiazolyl, pyrrolyl, oxazolyl, isoxazolyl, triazolyl, pyrimidinyl, quinolinyl, indolyl, benzimidazolyl, pyrazolyl and pyridyl, wherein R14 is optionally substituted at a substitutable position with one or more radicals independently selected from methylthio, methyl, ethyl, isopropyl, tert-butyl, isobutyl, pentyl, hexyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl, dichloropropyl, methoxy, methylenedioxy, ethoxy, propoxy, n-butoxy, hydroxymethyl, hydroxyethyl, methoxymethyl, ethoxymethyl, and trifluoromethoxy; or a pharmaceutically-acceptable salt thereof.
A family of specific compounds of particular interest within Formula V consists of compounds and pharmaceutically-acceptable salts thereof as follows:
3-[4-[[(methylphenyl)thio]methyl]-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;
4-[2-(pyrindin-3-yl)-4-[[(methylphenyl)thio]methyl]-1H-imidazol-1-yl]benzenesulfonamide;
3-(4-methyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;
4-[2-(6-methylpyrindin-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine;
4-[2-(4-methylpyrindin-3-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
3-methyl-2-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine;
1-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]isoquinoline;
4-[2-(3-methylpyrindin-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]quinoline;
4-[2-(2-thienyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
3-bromo-5-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyridine;
1-[4-(methylsulfonyl)phenyl]-2-(3-pyridinyl)-1H-imidazole-4-carbonitrile;
2-(2-methyloxazol-4-yl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
4-[2-(5-bromopyrindin-3-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
2-(5-methylpyridin-3-yl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole-4-carbonitrile;
3-(4-difluoromethyl-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl)pyridine;
4-[4-difluoromethyl-2-(pyrindin-3-yl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[4-cyano-2-(pyrindin-3-yl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[4-cyano-2-(5-methylpyrindin-3-yl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(2-quinolinyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
1-methyl-4-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]-1H-pyrazole;
4-[2-(1-methyl-1H-pyrazol-4-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
2-(1-methyl-1H-imidazol-4-yl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
4-[2-(1-methyl-1H-imidazol-4-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
2-(1-methyl-1H-imidazol-5-yl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
4-[2-(1-methyl-1H-imidazol-5-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
2-(1-methyl-1H-imidazol-2-yl)-1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazole;
4-[2-(1-methyl-1H-imidazol-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
1-[4-(methylsulfonyl)phenyl)-2-(4-methylthiazol-2-yl)-4-trifluoromethyl-1H-imidazole;
4-[2-(4-methylthiazol-2-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
1-[4-(methylsulfonyl)phenyl]-2-(2-methylthiazol-5-yl)-4-trifluoromethyl-1H-imidazole;
4-[2-(2-methylthiazol-5-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
5-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]isoxazole;
4-[2-(5-methylisoxazol-3-yl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
5-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]pyrimidine;
4-[2-(5-pyrimidinyl)-4-trifluoromethyl-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(pyrazin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(quinol-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
1-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-trifluoromethyl-1H-imidazol-2-yl]-1H-indole;
4-[2-(1-methylindol-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(isoquinol-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(2-methyloxazol-4-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(2-methylthiazol-4-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(oxazol-4-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(1-methylpyrazol-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(5-methylisoxazol-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methylpyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]thiophene;
3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]thiophene;
4-[2-(5-methylpyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
2-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-[2-(2-methylpyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(pyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
3-fluoro-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
3-chloro-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-[2-(5-fluoropyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;.
4-[2-(5-chloropyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
5-methyl-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-methyl-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
2-methoxy-6-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
5-methoxy-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-methoxy-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
2-chloro-6-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
5-chloro-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-chloro-2-[1-(4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
2-fluoro-6-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-fluoro-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-fluoro-2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-[2-(5-methylpyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methylpyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(6-methoxypyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(5-methoxypyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-methoxypyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(6-chloropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(5-chloropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-(2-(4-chloropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(6-fluoropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(5-fluoropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(4-fluoropyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
3-methoxy-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine-1-oxide;
3-[4-(4-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;
5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]-2-(methylthio)pyridine;
3-[4-(difluoromethyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazol-2-yl]pyridine;
4-[2-(5-methoxypyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[4-methyl-2-(3-pyridinyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3-pyridinyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide-1-oxide;
4-[4-(4-fluorophenyl)-2-(3-pyridinyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-(3-pyridinyl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide 1-oxide;
4-[4-(4-fluorophenyl)-2-(3-pyridinyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[2-[6-methylthio)pyridin-3-yl]-4-trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
4-[4-(difluoromethyl)-2-(3-pyridinyl)-1H-imidazol-1-yl]benzenesulfonamide;
3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
2-methyl-4-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
2-methyl-6-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-[2-(6-methylpyridin-3-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
1-methyl-3-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridinium iodide;
2-methyl-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine 1-oxide;
3-methyl-5-(1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
2-methoxy-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
2-[4-(4-fluorophenyl-1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
3-methyl-5-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine 1-oxide;
3-methoxy-5-[1-[4-(methylsulfonyl)phenyl)-4-(trifluoromethyl)-1H-imidazol-2-yl]pyridine;
4-[2-(3-methoxypyridin-5-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide;
2-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]quinoline;
2-[1-[4-(methylsulfonyl)phenyl)-4-(trifluoromethyl)-1H-imidazol-2-yl]pyrazine;
2-methyl-4-[1-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazol-2-yl]thiazole; and
4-[2-(5-methylpyridin-2-yl)-4-(trifluoromethyl)-1H-imidazol-1-yl]benzenesulfonamide.
Compounds of Formula V, especially where R14 is pyridyl, may form N-oxides, which may be active forms or prodrugs which would be converted to compounds of Formula V in vivo.
Compounds of Formula V would also be capable of inhibiting cytokines, such as TNF, IL-1, IL-6, and IL-8. As such, the compounds can be used in the manufacture of a medicament or in a method for the treatment for the prophylactic or therapeutic treatment of diseases mediated by cytokines, such as TNF, IL-1, IL-6, and IL-8.
The term xe2x80x9chydridoxe2x80x9d denotes a single hydrogen atom (H). This hydrido radical may be attached, for example, to an oxygen atom to form a hydroxyl radical, or two hydrido radicals may be attached to a carbon atom to form a methylene (xe2x80x94CH2xe2x80x94) radical. Where used, either alone or within other terms such as xe2x80x9chaloalkylxe2x80x9d, xe2x80x9calkylsulfonylxe2x80x9d, xe2x80x9calkoxyalkylxe2x80x9d and xe2x80x9chydroxyalkylxe2x80x9d, the term xe2x80x9calkylxe2x80x9d embraces linear or branched radicals having one to about twenty carbon atoms or, preferably, one to about twelve carbon atoms. More preferred alkyl radicals are xe2x80x9clower alkylxe2x80x9d radicals having one to about ten carbon atoms. Most preferred are lower alkyl radicals having one to about six carbon atoms. Examples of such radicals include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl, hexyl and the like. The term xe2x80x9chaloxe2x80x9d means halogens such as fluorine, chlorine, bromine or iodine. The term xe2x80x9chaloalkylxe2x80x9d embraces radicals wherein any one or more of the alkyl carbon atoms is substituted with halo as defined above. Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkyl radicals. A monohaloalkyl radical, for one example, may have either an iodo, bromo, chloro or fluoro atom within the radical. Dihalo and polyhaloalkyl radicals may have two or more of the same halo atoms or a combination of different halo radicals. xe2x80x9cLower haloalkylxe2x80x9d embraces radicals having one to six carbon atoms. Examples of haloalkyl radicals include fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, trichloromethyl, pentafluoroethyl, heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl, difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl. The term xe2x80x9chydroxyalkylxe2x80x9d embraces linear or branched alkyl radicals having one to about ten carbon atoms any one of which may be substituted with one or more hydroxyl radicals. More preferred hydroxyalkyl radicals are xe2x80x9clower hydroxyalkylxe2x80x9d radicals having one to six carbon atoms and one or more hydroxyl radicals. Examples of such radicals include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl and hydroxyhexyl. The terms xe2x80x9calkoxyxe2x80x9d and xe2x80x9calkoxyalkylxe2x80x9d embrace linear or branched oxy-containing radicals each having alkyl portions of one to about ten carbon atoms. More preferred alkoxy radicals are xe2x80x9clower alkoxyxe2x80x9d radicals having one to six carbon atoms. Examples of such radicals include methoxy, ethoxy, propoxy, butoxy and tert-butoxy. The term xe2x80x9calkoxyalkylxe2x80x9d, embraces alkyl radicals having one or more alkoxy radicals attached to the alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkyl radicals. More preferred alkoxyalkyl radicals are xe2x80x9clower alkoxyalkylxe2x80x9d radicals having one to six carbon atoms and one or two alkoxy radicals. Examples of such radicals include methoxymethyl, methoxyethyl, ethoxyethyl, methoxybutyl and methoxypropyl. The xe2x80x9calkoxyxe2x80x9d or xe2x80x9calkoxyalkylxe2x80x9d radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide xe2x80x9chaloalkoxyxe2x80x9d or xe2x80x9chaloalkoxyalkylxe2x80x9d radicals. More preferred haloalkoxy radicals are xe2x80x9clower haloalkoxyxe2x80x9d radicals having one to six carbon atoms and one or more halo radicals. Examples of such radicals include fluoromethoxy, chloromethoxy, trifluoromethoxy, trifluoroethoxy, fluoroethoxy and fluoropropoxy. The term xe2x80x9ccyanoalkylxe2x80x9d embraces radicals having a cyano or nitrile (xe2x80x94CN) radical attached to an alkyl radical as described above. More preferred cyanoalkyl radicals are xe2x80x9clower cyanoalkylxe2x80x9d radicals having one to six carbon atoms. Examples of such lower cyanoalkyl radicals include cyanomethyl, cyanopropyl, cyanoethyl and cyanobutyl. The term xe2x80x9ccycloalkylxe2x80x9d embraces saturated carbocyclic radicals having three to twelve carbon atoms. More preferred cycloalkyl radicals are xe2x80x9clower cycloalkylxe2x80x9d radicals having three to about eight carbon atoms. Examples of such radicals include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl. The term xe2x80x9ccycloalkenylxe2x80x9d embraces unsaturated cyclic radicals having three to ten carbon atoms. More preferred cycloalkenyl radicals are xe2x80x9clower cycloalkenylxe2x80x9d radicals having about five to about eight carbon atoms. Examples of such radicals include cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl The term xe2x80x9carylxe2x80x9d, alone or in combination, means a carbocyclic aromatic system containing one, two or three rings wherein such rings may be attached together in a pendent manner or may be fused. The term xe2x80x9carylxe2x80x9d embraces aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indane and biphenyl. Such aryl radicals may be substituted at a substitutable position with one or more substituents selected from halo, alkylthio, alkylsulfinyl, alkyl, cyano, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl and haloalkoxy. The terms xe2x80x9cheterocyclicxe2x80x9d and xe2x80x9cheterocycloxe2x80x9d embraces saturated, partially saturated and unsaturated heteroatom-containing ring-shaped radicals, where the heteroatoms may be selected from nitrogen, sulfur and oxygen. Examples of saturated heterocyclo radicals include saturated 3 to 6-membered heteromonocylic group containing 1 to 4 nitrogen atoms [e.g. pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.]; saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. morpholinyl, etc.]; and saturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., thiazolidinyl, etc.]. Examples of partially saturated heterocyclic radicals include dihydrothiophene, dihydropyran, dihydrofuran and dihydrothiazole. The term xe2x80x9cheteroarylxe2x80x9d, embraces unsaturated heterocyclic radicals. Examples of xe2x80x9cheteroarylxe2x80x9d radicals include unsaturated 3 to 6 membered heteromonocyclic group containing 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl, pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl [e.g., 4 H-1,2,4-triazolyl, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.] tetrazolyl [e.g. 1H-tetrazolyl, 2H-tetrazolyl, etc.], etc.; unsaturated condensed heterocyclic group containing 1 to 5 nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl (quinolinyl), isoquinolyl (isoquinolinyl), indazolyl, benzotriazolyl, tetrazolopyridazinyl [e.g., tetrazolo [1,5-b]pyridazinyl, etc.], etc.; unsaturated 3 to 6-membered heteromonocyclic group containing an oxygen atom, for example, pyranyl, 2-furyl, 3-furyl, etc.; unsaturated 3 to 6-membered heteromonocyclic group containing a sulfur atom, for example, 2-thienyl, 3-thienyl, etc.; unsaturated 3- to 6-membered heteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl [e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, etc.] etc.; unsaturated condensed heterocyclic group containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g. benzoxazolyl, benzoxadiazolyl, etc.]; unsaturated 3 to 6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl, thiadiazolyl [e.g., 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.] etc.; unsaturated condensed heterocyclic group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., benzothiazolyl, benzothiadiazolyl, etc.] and the like. The term also embraces radicals where heterocyclic radicals are fused with aryl radicals. Examples of such fused bicyclic radicals include benzofuran, benzothiophene, and the like. Said heterocyclo may be substituted at a substitutable position with one or more substituents selected from halo, alkylthio, alkylsulfinyl, alkyl, cyano, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl and haloalkoxy. More preferred heteroaryl radicals include five to six membered heteroaryl radicals. The term xe2x80x9cheterocycloalkylxe2x80x9d embraces heterocyclic-substituted alkyl radicals. More preferred heterocycloalkyl radicals are xe2x80x9clower heterocycloalkylxe2x80x9d radicals having one to six carbon atoms and a heterocyclic radical. Examples include such radicals as pyrrolidinylmethyl. The term xe2x80x9cheteroarylalkylxe2x80x9d embraces heteroaryl-substituted alkyl radicals. More preferred heteroarylalkyl radicals are xe2x80x9clower heteroarylalkylxe2x80x9d radicals having one to six carbon atoms and a heteroaryl radical. Examples include such heteroarylalkyl radicals such as pyridylmethyl and thienylmethyl. The term xe2x80x9calkylthioxe2x80x9d embraces radicals containing a linear or branched alkyl radical, of one to about ten carbon atoms attached to a divalent sulfur atom. More preferred alkylthio radicals are xe2x80x9clower alkylthioxe2x80x9d radicals having alkyl radicals of one to six carbon atoms. Examples of such lower alkylthio radicals are methylthio, ethylthio, propylthio, butylthio and hexylthio. The term xe2x80x9calkylthioalkylxe2x80x9d embraces alkylthio radicals attached to an alkyl radical. More preferred alkylthioalkyl radicals are xe2x80x9clower alkylthioalkylxe2x80x9d radicals having alkyl radicals of one to six carbon atoms and an alkylthio radical as described above. Examples of such radicals include methylthiomethyl. The term xe2x80x9carylthioxe2x80x9d embraces radicals containing an aryl radical, attached to a divalent sulfur atom, such as a phenylthio radical. The term xe2x80x9carylthioalkylxe2x80x9d embraces arylthio radicals attached to an alkyl radical. More preferred arylthioalkyl radicals are xe2x80x9clower arylthioalkylxe2x80x9d, radicals having alkyl radicals of one to six carbon atoms and an arylthio radical as described above. Examples of such radicals include phenylthiomethyl, where the phenyl radical may be substituted as described above. The term xe2x80x9calkylsulfinylxe2x80x9d embraces radicals containing a linear or branched alkyl radical, of one to ten carbon atoms, attached to a divalent xe2x80x94S(xe2x95x90O)xe2x80x94 radical. More preferred alkylsulfinyl radicals are xe2x80x9clower alkylsulfinylxe2x80x9d radicals having one to six carbon atoms. Examples of such lower alkylsulfinyl radicals include methylsulfinyl, ethylsulfinyl, butylsulfinyl and hexylsulfinyl. The term xe2x80x9csulfonylxe2x80x9d, whether used alone or linked to other terms such as alkylsulfonyl, denotes respectively divalent radicals xe2x80x94SO2xe2x80x94. xe2x80x9cAlkylsulfonylxe2x80x9d embraces alkyl radicals attached to a sulfonyl radical, where alkyl is defined as above. More preferred alkylsulfonyl radicals are xe2x80x9clower alkylsulfonylxe2x80x9d radicals having one to six carbon atoms. Examples of such lower alkylsulfonyl radicals include methylsulfonyl, ethylsulfonyl and propylsulfonyl. The xe2x80x9calkylsulfonylxe2x80x9d radicals may be further substituted with one or more halo atoms, such as fluoro, chloro or bromo, to provide xe2x80x9chaloalkylsulfonylxe2x80x9d radicals. More preferred haloalkylsulfonyl radicals are xe2x80x9clower haloalkylsulfonylxe2x80x9d radicals having one or more halo atoms attached to lower alkylsulfonyl radicals as described above. Examples of such lower haloalkylsulfonyl radicals include fluoromethylsulfonyl, trifluoromethylsulfonyl and chloromethylsulfonyl. The term xe2x80x9carylsulfonylxe2x80x9d embraces aryl radicals as defined above, attached to a sulfonyl radical. Examples of such radicals include phenylsulfonyl. The terms xe2x80x9csulfamylxe2x80x9d, xe2x80x9caminosulfonylxe2x80x9d and xe2x80x9csulfonamidylxe2x80x9d denotes NH2O2Sxe2x80x94. The term xe2x80x9cacylxe2x80x9d denotes a radical provided by the residue after removal of hydroxyl from an organic acid. Examples of such acyl radicals include formyl, alkanoyl and aroyl radicals. The alkanoyl radicals may be substituted or unsubstituted, such as formyl, acetyl, propanoyl, butanoyl, isobutanoyl, valeryl, isovaleryl, pivaloyl, hexanoyl or the like. The terms xe2x80x9ccarboxyxe2x80x9d or xe2x80x9ccarboxylxe2x80x9d, whether used alone or with other terms, such as xe2x80x9ccarboxyalkylxe2x80x9d, denotes xe2x80x94CO2H. The term xe2x80x9ccarbonylxe2x80x9d, whether used alone or with other terms, such as xe2x80x9calkoxycarbonylxe2x80x9d, denotes xe2x80x94(Cxe2x95x90O)xe2x80x94. The term xe2x80x9calkoxycarbonylxe2x80x9d means a radical containing an alkoxy radical, as defined above, attached via an oxygen atom to a carbonyl radical. Preferably, xe2x80x9clower alkoxycarbonylxe2x80x9d embraces alkoxy radicals having one to six carbon atoms. Examples of such xe2x80x9clower alkoxycarbonylxe2x80x9d ester radicals include substituted or unsubstituted methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl and hexyloxycarbonyl. The term xe2x80x9caralkylxe2x80x9d embraces aryl-substituted alkyl radicals. Preferable aralkyl radicals are xe2x80x9clower aralkylxe2x80x9d radicals having aryl radicals attached to alkyl radicals having one to six carbon atoms. Examples of such phenylalkyl radicals include benzyl, diphenylmethyl, triphenylmethyl, phenylethyl and diphenylmethyl. The aryl in said aralkyl radicals may be substituted at a substitutable position with one or more substituents selected from halo, alkylthio, alkylsulfinyl, alkyl, cyano, haloalkyl, hydroxyl, alkoxy, hydroxyalkyl and haloalkoxy. The terms benzyl and phenylmethyl are interchangeable. The terms xe2x80x9calkylcarbonylxe2x80x9d, xe2x80x9carylcarbonylxe2x80x9d and xe2x80x9caralkylcarbonylxe2x80x9d include radicals having alkyl, aryl and aralkyl radicals, respectively, as defined above, attached to a carbonyl radical. More preferred alkylcarbonyl radicals are xe2x80x9clower alkylcarbonylxe2x80x9d radicals having one to six carbon atoms. Examples of such radicals include methylcarbonyl and ethylcarbonyl. More preferred aralkylcarbonyl radicals are xe2x80x9clower aralkylcarbonylxe2x80x9d radicals having aryl radicals attached to alkyl radicals having one to six carbon atoms. Examples of such aralkylcarbonyl radicals include benzylcarbonyl. An example of an arylcarbonyl radical is phenylcarbonyl. The term xe2x80x9calkoxycarbonylalkylxe2x80x9d embraces radicals having xe2x80x9calkoxycarbonylxe2x80x9d, as defined above attached to an alkyl radical. More preferred alkoxycarbonylalkyl radicals are xe2x80x9clower alkoxycarbonylalkylxe2x80x9d, having lower alkoxycarbonyl radicals as defined above attached to one to six carbon atoms. Examples of such lower alkoxycarbonylalkyl radicals include methoxycarbonylmethyl. The term xe2x80x9chaloalkylcarbonylxe2x80x9d embraces radicals having a haloalkyl radical as described above attached to a carbonyl radical. More preferred radicals are xe2x80x9clower haloalkylcarbonylxe2x80x9d radicals where lower haloalkyl radicals, as described above are attached to a carbonyl radical. The term xe2x80x9ccarboxyalkylxe2x80x9d embraces radicals having a carboxy radical as defined above, attached to an alkyl radical. More preferred carboxyalkyl radicals are xe2x80x9clower carboxyalkylxe2x80x9d radicals having one or more carboxy radicals attached to an alkyl radical having one to six carbon atoms. The term xe2x80x9cheteroaralkylxe2x80x9d embraces heteroaryl-substituted alkyl radicals. More preferred heteroaralkyl radicals are xe2x80x9clower heteroaralkylxe2x80x9d radicals having five to six membered heteroaryl radicals attached to one to six carbon atoms. Examples of such radicals include pyridylmethyl, quinolylmethyl, thienylmethyl, furylethyl and quinolylethyl. The heteroaryl in said heteroaralkyl may be additionally substituted with halo, alkyl, alkoxy, halkoalkyl and haloalkoxy. The term xe2x80x9caryloxyxe2x80x9d embraces aryl radicals, as defined above, attached to an oxygen atom. Examples of such radicals include phenoxy. The term xe2x80x9cheteroaryloxyxe2x80x9d embraces heteroaryl radicals as defined above attached to an oxygen radical. More preferred heteroaryloxy radicals are xe2x80x9clower heteroaryloxyxe2x80x9d radicals having five to six membered heteroaryl radicals. The term xe2x80x9caralkoxyxe2x80x9d embraces oxy-containing aralkyl radicals attached through the oxygen atom to other radicals. The term xe2x80x9caralkoxyalkylxe2x80x9d embraces alkyl radicals having one or more aralkoxy radicals attached to the alkyl radical, that is, to form monoaralkyloxyalkyl and diaralkyloxyalkyl radicals. The xe2x80x9caralkoxyxe2x80x9d or xe2x80x9caralkoxyalkylxe2x80x9d radicals may be further substituted on the aryl ring portion of the radical. More preferred aralkoxyalkyl radicals are xe2x80x9clower arakoxyalkylxe2x80x9d having an alkoxy attached to one to six carbon atoms. Examples of lower aralkoxyalkyl radicals include benzyloxymethyl. The term xe2x80x9ccycloalkylthioxe2x80x9d embraces radicals containing a cycloalkyl radical, of three to about ten carbon atoms attached to a divalent sulfur atom. More preferred cycloalkylthio radicals are xe2x80x9clower cycloalkylthioxe2x80x9d radicals having cycloalkyl radicals of four to six carbon atoms. Examples of such lower cycloalkylthio radicals are cyclobutylthio, cyclopentylthio and cyclohexylthio. The term xe2x80x9ccycloalkylthioalkylxe2x80x9d embraces radicals containing a cycloalkylthio radical, as described above, attached to an alkyl radical. More preferred cycloalkylthioalkyl radicals are xe2x80x9clower cycloalkylthioalkylxe2x80x9d radicals having cycloalkyl radicals of four to six carbon atoms and alkyl radicals of one to six carbons. The term xe2x80x9ccycloalkylsulfonylxe2x80x9d embraces radicals containing a cycloalkyl radical, of three to about ten carbon atoms attached to a divalent sulfonyl radical. More preferred cycloalkylsulfonyl radicals are xe2x80x9clower cycloalkylsulfonylxe2x80x9d radicals having cycloalkyl radicals of four to six carbon atoms. Examples of such lower cycloalkylsulfonyl radicals are cyclobutylsulfonyl, cyclopentylsulfonyl and cyclohexylsulfonyl. The term xe2x80x9ccycloalkylsulfonylalkylxe2x80x9d embraces radicals containing a cycloalkylsulfonyl radical, as described above, attached to an alkyl radical. More preferred cycloalkylsulfonylalkyl radicals are xe2x80x9clower cycloalkylsulfonylalkylxe2x80x9d radicals having cycloalkyl radicals of four to six carbon atoms and alkyl radicals of one to six carbons. The term xe2x80x9ccycloalkyloxyxe2x80x9d embraces radicals containing a cycloalkyl radical, of three to about ten carbon atoms attached to a divalent oxygen atom. More preferred cycloalkyloxy radicals are xe2x80x9clower cycloalkyloxyxe2x80x9d radicals having cycloalkyl radicals of four to six carbon atoms. Examples of such lower cycloalkyloxy radicals are cyclobutyloxy, cyclopentyloxy and cyclohexyloxy. The term xe2x80x9ccycloalkyloxyalkylxe2x80x9d embraces radicals containing a cycloalkyloxy radical, as described above, attached to an alkyl radical. More preferred cycloalkyloxyalkyl radicals are xe2x80x9clower cycloalkyloxyalkylxe2x80x9d radicals having cycloalkyl radicals of four to six carbon atoms and alkyl radicals of one to six carbons. The term xe2x80x9cheteroarylthioxe2x80x9d embraces radicals having heteroaryl radicals attached to a sulfur radical. More preferred heteroarylthio radicals are xe2x80x9clower heteroarylthioxe2x80x9d radicals having five to six membered heteroaryl radicals. Examples of such radicals include 2-furylthio, 2-thienylthio, 3-thienylthio, 4-pyridylthio and 3-pyridylthio. The term xe2x80x9cheteroarylalkylthioxe2x80x9d denotes radicals having an heteroaryl radical attached to an alkylthio radical. More preferred heteroarylalkylthio radicals are xe2x80x9clower heteroarylalkylthioxe2x80x9d radicals having heteroaryl radicals attached to lower alkylthio radicals as described above. Examples of such radicals include furylmethylthio and quinolylmethylthio. The term xe2x80x9cheteroarylalkylthioalkylxe2x80x9d denotes radicals having an heteroaryl radical attached to an alkylthio radical further attached through the sulfur atom to an alkyl radical. More preferred heteroarylalkylthioalkyl are xe2x80x9clower heteroarylalkylthioalkylxe2x80x9d radicals having lower heteroarylalkyl radicals as described above. Examples of such radicals include furylmethylthiomethyl and quinolylmethylthioethyl. The term xe2x80x9cheteroarylthioalkylxe2x80x9d denotes radicals having an heteroaryl radical attached to a sulfur atom further attached through the sulfur atom to an alkyl radical. More preferred heteroarylthioalkyl radicals are xe2x80x9clower heteroarylthioalkylxe2x80x9d having lower heteroarylthio radicals as described above. Examples of such radicals include thienylthiomethyl and pyridylthiohexyl. The term xe2x80x9caralkylthioxe2x80x9d embraces radicals having aralkyl radicals attached to a bridging sulfur atom. More preferred aralkylthio radicals are xe2x80x9clower aralkylthioxe2x80x9d radicals having the aryl radicals attached to one to six carbon atoms. Examples of such radicals include benzylthio and phenylethylthio. The term xe2x80x9caralkylthioalkylxe2x80x9d embraces radicals having aralkyl radicals attached to alkyl radicals through a bridging sulfur atom. More preferred aralkylthioalkyl radicals are xe2x80x9clower aralkylthioalkylxe2x80x9d radicals having the aralkylthio radicals attached to one to six carbon atoms. Examples of such radicals include benzylthiomethyl and phenylethylthiomethyl. The term xe2x80x9cheteroaryloxyalkylxe2x80x9d denotes radicals having an heteroaryl radical attached to an oxygen atom further attached through the oxygen atom to an alkyl radical. More preferred heteroaryloxyalkyl radicals are xe2x80x9clower heteroaryloxyalkylxe2x80x9d radicals having five to six membered heteroaryl radicals. Examples of such radicals include furyloxyethyl, pyridyloxymethyl and thienyloxyhexyl. The term xe2x80x9caminoalkylxe2x80x9d embraces alkyl radicals substituted with amino radicals. More preferred aminoalkyl radicals are xe2x80x9clower aminoalkylxe2x80x9d having one to six carbon atoms. Examples include aminomethyl, aminoethyl and aminobutyl. The term xe2x80x9calkylaminoalkylxe2x80x9d embraces aminoalkyl radicals having the nitrogen atom substituted with at least one alkyl radical. More preferred alkylaminoalkyl radicals are xe2x80x9clower alkylaminoalkylxe2x80x9d having one to six carbon atoms attached to a lower aminoalkyl radical as described above. The term xe2x80x9calkylaminoxe2x80x9d denotes amino groups which have been substituted with one or two alkyl radicals. More preferred alkylamino radicals are xe2x80x9clower alkylaminoxe2x80x9d radicals having one or two alkyl radicals of one to six carbon atoms, attached to a nitrogen atom. Suitable xe2x80x9calkylaminoxe2x80x9d may be mono or dialkylamino such as N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylamino and the like. TThe term xe2x80x9caminocarbonylxe2x80x9d denotes an amide group of the formula xe2x80x94C(xe2x95x90O)NH2. he term xe2x80x9calkylaminocarbonylxe2x80x9d embraces alkylamino radicals, as described above, to a carbonyl radical. More preferred alkylaminocarbonyl radicals are xe2x80x9clower alkylaminocarbonylxe2x80x9d having lower alkylamino radicals, as described above, attached to a carbonyl radical. Examples of such radicals include N-methylaminocarbonyl and N,N-dimethylaminocarbonyl. The term xe2x80x9carylaminoxe2x80x9d denotes amino groups which have been substituted with one or two aryl radicals, such as N-phenylamino. The xe2x80x9carylaminoxe2x80x9d radicals may be further substituted on the aryl ring portion of the radical. The terms xe2x80x9cN-arylaminoalkylxe2x80x9d and xe2x80x9cN-aryl-N-alkylaminoalkylxe2x80x9d denote amino groups which have been substituted with one aryl radical or one aryl and one alkyl radical, respectively, and having the amino group attached to an alkyl radical. More preferred arylaminoalkyl radicals are xe2x80x9clower arylaminoalkylxe2x80x9d having the arylamino radical attached to one to six carbon atoms. Examples of such radicals include N-phenylaminomethyl and N-phenyl-N-methylaminomethyl. The term xe2x80x9calkylaminocarbonylalkylxe2x80x9d denotes an alkylaminocarbonyl group which is attached to an alkyl radical. More preferred are xe2x80x9clower alkylaminocarbonylalkylxe2x80x9d having lower alkylaminocarbonyl radicals as described above attached to one to six carbon atoms. The term xe2x80x9caryloxyalkylxe2x80x9d embraces alkyl radicals having one or more aryloxy radicals, aryl radicals attached to a divalent oxygen atom, attached to the alkyl radical, that is, to form monoaryloxyalkyl and diaryloxyalkyl radicals. The more preferred aryloxyalkyl radicals are xe2x80x9clower aryloxyalkylxe2x80x9d radicals having aryloxy radicals attached to one to six carbon atoms. Examples include phenoxymethyl. The term xe2x80x9cheteroarylalkoxyxe2x80x9d embraces radicals having one or more heteroaryl radicals attached to an alkoxy radical. More preferred heteroarylalkoxy radicals are xe2x80x9clower heteroarylalkoxyxe2x80x9d radicals having five to six membered heteroaryl radicals. Examples of such radicals include 2-thienylmethoxy, 3-thienylmethoxy, 2-furylmethoxy, 3-furylmethoxy and 2-pyridylmethoxy, 3-pyridylmethoxy, 4-pyridylmethoxy. The term xe2x80x9cheteroarylalkoxyalkylxe2x80x9d embraces alkyl radicals having one or more heteroaryl radicals attached to an alkoxy radical, further attached to the alkyl radical. More preferred heteroarylalkoxyalkyl radicals are xe2x80x9clower heteroarylalkoxyalkyl radicals having five to six membered heteroaryl radicals. Examples of such radicals include 2-thienylmethoxymethyl. The term xe2x80x9cazidoalkylxe2x80x9d denotes alkyl radicals substituted with azido groups (xe2x80x94N3). More preferred azidoalkyl radicals are xe2x80x9clower azidoalkylxe2x80x9d having one to six carbon atoms. Examples include azidomethyl, azidoethyl and aminopropyl.
The present invention comprises a pharmaceutical composition comprising a therapeutically-effective amount of a compound of Formula I in association with at least one pharmaceutically-acceptable carrier, adjuvant or diluent.
The present invention also comprises a method of treating inflammation or inflammation-associated disorders in a subject, the method comprising treating the subject having or susceptible to such inflammation or disorder with a therapeutically-effective amount of a compound of Formula I.
Also included in the family of compounds of Formula I are the stereoisomers thereof. Compounds of the present invention can possess one or more asymmetric carbon atoms and are thus capable of existing in the form of optical isomers as well as in the form of racemic or nonracemic mixtures thereof. Accordingly, some of the compounds of this invention may be present in racemic mixtures which are also included in this invention. The optical isomers can be obtained by resolution of the racemic mixtures according to conventional processes, for example by formation of diastereoisomeric salts by treatment with an optically active acid or base. Examples of appropriate acids are tartaric, diacetyltartaric, dibenzoyltartaric, ditoluoyltartaric and camphorsulfonic acid and then separation of the mixture of diastereoisomers by crystallization followed by liberation of the optically active bases from these salts. A different process for separation of optical isomers involves the use of a chiral chromatography column optimally chosen to maximize the separation of the enantiomers. Still another available method involves synthesis of covalent diastereoisomeric molecules by reacting an amine functionality of precursors to compounds of Formula I with an optically pure acid in an activated form or an optically pure isocyanate. Alternatively, diastereomeric derivatives can be prepared by reacting a carboxyl functionality of precursors to compounds of Formula I with an optically pure amine base. The synthesized diastereoisomers can be separated by conventional means such as chromatography, distillation, crystallization or sublimation, and then hydrolyzed to deliver the enantiomerically pure compound. The optically active compounds of Formula I can likewise be obtained by utilizing optically active starting materials. These isomers may be in the form of a free acid, a free base, an ester or a salt.
Also included in the family of compounds of Formula I are the pharmaceutically-acceptable salts thereof. The term xe2x80x9cpharmaceutically-acceptable saltsxe2x80x9d embraces salts commonly used to form alkali metal salts and to form addition salts of free acids or free bases. The nature of the salt is not critical, provided that it is pharmaceutically-acceptable. Suitable pharmaceutically-acceptable acid addition salts of compounds of Formula I may be prepared from an inorganic acid or from an organic acid. Examples of such inorganic acids are hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric and phosphoric acid. Appropriate organic acids may be selected from aliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic, carboxylic and sulfonic classes of organic acids, example of which are formic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic, tartaric, citric, ascorbic, glucuronic, maleic, fumaric, pyruvic, aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic, p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic), methanesulfonic, ethylsulfonic, benzenesulfonic, pantothenic, toluenesulfonic, 2-hydroxyethanesulfonic, sulfanilic, stearic, cyclohexylaminosulfonic, algenic, xcex2-hydroxybutyric, salicylic, galactaric and galacturonic acid. Suitable pharmaceutically-acceptable base addition salts of compounds of Formula I include metallic salts made from aluminum, calcium, lithium, magnesium, potassium, sodium and zinc or organic salts made from N,Nxe2x80x2-dibenzylethylenediamine, choline, chloroprocaine, diethanolamine, ethylenediamine, meglumine (N-methylglucamine) and procaine. All of these salts may be prepared by conventional means from the corresponding compound of Formula I by reacting, for example, the appropriate acid or base with the compound of Formula I.
Racemic alcohol containing compounds may be resolved to their single enantiomers by the following procedure. Treatment of the racemic alcohols with an acetylating agent, such as vinyl acetate or isopropenyl acetate, in the presence of an appropriate enzyme results in the selective acetylation of one of the constituent enantiomeric alcohols, leading to a crude product consisting of essentially enantiomerically pure alcohol. Appropriate enzymes include, but are not limited to, lipases (such as AMANO Lipase PS30), cholinesterases and proteases. The reaction may be monitored to complete acetylation of one of the enantiomers using HPLC. The enantiomerically pure alcohol may be separated from enantiomerically pure acetate by column chromatography. Saponification of the acetate using aqueous base provides the other enantiomerically pure alcohol.
Alternatively, alcohols can be resolved via procedures outlined in E. Eliel and S. Wilen, Stereochemistry of organic compounds, 337-340 (1994).
The compounds of the invention can be synthesized according to the following procedures of Schemes I-XV, wherein the R1-R14 substituents are as defined for Formula I-V, above, except where further noted. 
Scheme I shows the three step preparation of the 4,5-dihydro-imidazoles 5 and substituted imidazoles 6 of the present invention. In step 1, the reaction of substituted nitrites (R2CN) 1 with primary amines (R1NH2) 2 in the presence of alkylaluminum reagents such as trimethylaluminum, triethylaluminum, dimethylaluminum chloride, diethylaluminum chloride in the presence of inert solvents such as toluene, benzene and xylene, gives amidines 3. In step 2, the reaction of amidine 3 with 2-halo-ketones 4 (where X is Br or Cl) in the presence of bases, such as sodium bicarbonate, potassium carbonate, sodium carbonate, potassium bicarbonate or hindered tertiary amines such as N,Nxe2x80x2-diisopropylethylamine, gives the 4,5-dihydroimidazoles 5 (where R5 is hydroxyl and R6 is hydrido). Some of the suitable solvents for this reaction are isopropanol, acetone and dimethylformamide. The reaction may be carried out at temperatures of about 20xc2x0 C. to about 90xc2x0 C. In step 3, the 4,5-dihydroimidazoles 5 may be dehydrated in the presence of an acid catalyst such as 4-toluenesulfonic acid or mineral acids to form the 1,2-disubstituted imidazoles 6 of the invention. Suitable solvents for this dehydration step are e.g., toluene, xylene and benzene. Trifluoroacetic acid can be used as solvent and catalyst for this dehydration step.
In some cases (e.g., where R3=methyl or phenyl) the intermediate 5 may not be readily isolable. The reaction, under the conditions described above, proceeds to give the targeted imidazoles directly. 
Scheme II shows alternative methods of forming amidines 3. Amidines 3 are also available by the two step conversion of amide 7 (R2CONHR1 formed by the conversion of primary amine 2). In Step 1, the amide 7 is converted to the corresponding imidoyl chloride by treatment with a halogenating agent such as phosphorus oxychloride. In step two, treatment of the imidoyl chloride with ammonia forms the desired amidine 3. In addition, amidines 3 may also be obtained by conversion of primary amides 8 (e. g., R2CONH2) or nitrites 1 (R2CN) to their corresponding iminothioethers or iminoethers 9 (where X is sulfur and oxygen, respectively) followed by reaction with amine 2. 
Scheme III shows the two step method of preparing certain 2-halo-ketones 12 (compound 4 from Scheme I where X is bromo or chloro, R3 is xe2x80x94CH2YRxe2x80x2 [Y is oxygen, sulfur or xe2x80x94NH] and R4 is hydrido) which are not commercially available, from 1,2-dihalopropenes 10. In step 1, 2,3-dichloro-1-propene 10 is added to a mixture of alcohol, amine or mercaptan (Rxe2x80x2YH) and base, such as potassium carbonate in acetone, to form the 2-chloropropene 11, where Rxe2x80x2 is an alkyl or aryl group and Y is an oxygen, nitrogen or sulfur atom. In step 2, the 2-chloropropene 11 is converted to 2-haloketones 12 via a method as described by H. E. Morton and M. R. Leanna (Tet. Letters, 34, 4481 (1993)). 
Scheme IV shows a method of forming 2-chloropropenes 14 (compound 11 in Scheme III where Y is oxygen). The 2-chloro-2-propen-1-ol 13 is added to a mixture of an alkyl, aralkyl or heteroaralkyl halide (XRxe2x80x2) and base, such as potassium carbonate in acetone, to form the 2-chloropropene 14.
Alternatively, 2-chloropropenes 14 can be formed from the corresponding 2,3-dichloro-1-propenes 10 (Scheme III) by reaction with a metal alkoxide in an appropriate solvent. Sodium methoxide in methanol is an example of one such alkoxide and solvent. 
Scheme V shows the three step preparation of 1,2-diarylimidazoles 20 of the present invention. In step 1, the reaction of substituted benzonitriles 15 with substituted anilines 16 in the presence of alkylaluminum reagents such as trimethylaluminum, triethylaluminum, dimethylaluminum chloride, diethylaluminum chloride gives amidines 17. In step 2, the reaction of amidines 17 with haloketones 18 (compound 4 in Scheme I where X is Br or Cl and R4 is hydrido) in the presence of bases, such as sodium bicarbonate, potassium carbonate, sodium carbonate, potassium bicarbonate or hindered tertiary amines such as N,Nxe2x80x2-diisopropylethylamine, gives the 1,2-diaryl-4,5-dihydro-imidazoles 19. Some of the suitable solvents for this reaction are isopropanol, acetone and dimethylformamide. The reaction may be carried out at a temperature between about 20xc2x0 C. to about 90xc2x0 C. In step 3, the 1,2-diaryl-4,5-dihydro-imidazoles 19 may be dehydrated in the presence of an acid catalyst such as 4-toluenesulfonic acid to form the 1,2-diarylimidazoles 20 of the present invention. Suitable solvents for this dehydration step are, for example, toluene, xylene and benzene. Trifluoroacetic acid can be used as solvent and catalyst for this dehydration step.
In some cases (e.g., where R3 is methyl or phenyl), the intermediate 19 may not be readily isolable. The reaction, under the conditions described above, proceeds to give the targeted imidazoles 20 directly. 
Scheme VI shows the formation of 4-hydroxymethyl imidazoles 22 and 4-formyl-imidazoles 23 from benzyloxy-protected imidazoles 21 and from 4-carboalkoxy imidazoles 23. in step 1, the oxidative deprotection of 4-methoxybenzyl group in 21, such as with ceric ammonium nitrate, gives the hydroxymethyl imidazoles 22. Alternatively, the alkoxycarbonyl group of 23 may be reduced to the hydroxymethyl group. Suitable reducing agents include lithium borohydride. In step 2, the hydroxymethyl imidazoles 22 are oxidized, for example, with pyridinium chlorochromate, to give the 4-formyl-imidazoles 24. 
Scheme VII shows the formation of 4-difluoromethyl-imidazoles 25 from 4-formyl-imidazoles 24. The 4-formyl-imidazoles 24 are converted to desired 4-difluoromethyl-imidazoles 25 by direct fluorination using the known reagents such as SF4 or diethylaminosulfur trifluoride (DAST). For discussion of the reaction and the representative procedures, see e.g., Organic Reactions, 34, 319 (1987), Organic Reactions, 35, 513 (1988), Organic Reactions, 21, 319 (1974) and Chem. Soc. Reviews, 16, 381 (1987), Alternatively, the imidazoles 25 can be synthesized by reaction of hydrazones of 24 with N-bromosuccinimide/pyridinium poly(hydrogen fluoride). This transformation has been developed by Olah and co-workers (see, Synlett, 594 (1990)]. 
Scheme VIII shows the conversion of the 4-formyl-imidazoles 24 to 4-cyanoimidazoles 26. The 4-formyl-imidazoles 24 are converted to the target nitrile derivatives 26 by following the literature procedures [see, e.g., Chem. Letters, 773 (1984), Synthesis, 510 (1984), Tetrahedron Lett., 1781 (1976), Synthesis, 739 (1981), Synth. Communications, 18, 2179 (1988), Bull. Chem. Soc. Japan, 54, 1579 (1981), Synthesis, 201 (1985), Synthesis, 190 (1982), Synthesis, 56 (1979), and the references cited therein]. 
Scheme IX shows other 1,2-diarylimidazoles that can be synthesized from the 4-formyl-imidazoles 24 in two steps. In step 1, the 4-formyl-imidazoles 24 are converted to carbinol derivatives (where R is aralkyl or alkyl) by addition of Grignard reagents (RMgBr). In step 2, the hydroxy derivatives 27 are reduced by catalytic hydrogenation (using e.g., Pd/C or Pt/C), preferably in the presence of a small amount of acid (e.g., acetic acid or aqueous HCl) to form the alkyl or aralkyl derivatives 28. Alternatively, the ketones 29 are synthesized by oxidation (e.g., using pyridinium chlorochromate) of the hydroxy derivatives 27. 
Synthetic Scheme X shows the three step procedure used to prepare sulfonamide antiinflammatory agents 31 and the two step procedure used to prepare fluoromethyl sulfone antiinflammatory agents 32 from their corresponding methyl sulfones 30. In step one, THF solutions of the methyl sulfones 30 at xe2x88x9278xc2x0 C. are treated with a base such as alkyllithium reagents, lithioamides and Grignard reagents. Examples of such bases include n-butyllithium, methyllithium, lithium diisopropylamide (LDA), butylmagnesium chloride, phenylmagnesium bromide and methylmagnesium chloride. In step two, the anions generated in step one are treated with an organoborane, e.g., triethylborane, tributylborane, etc., at xe2x88x9278xc2x0 C. then warmed to ambient temperature prior to stirring at reflux. An alternative to the boron chemistry involves room temperature alkylation, such as with haloalkyltrialkylsilanes, followed by treatment with silylalkyl-elimination agents. Examples of such haloalkyltrialkylsilanes include trimethylsilylmethylhalides such as (iodomethyl)trimethylsilane and (chloromethyl)trimethylsilane. Suitable silylalkyl-elimination agents include compounds which produce a fluoride ion. Examples of such compounds include alkylammonium fluorides and cesium fluoride. Tetrabutylammonium fluoride (1M in THF) is preferred. The deprotonation of sulfone is conveniently carried out in the temperature range of about xe2x88x9270xc2x0 C. to about 25xc2x0 C., preferably at about 0xc2x0 C. The formation of silylalkylsulfone is conveniently carried out in the temperature range of about 0xc2x0 C. to about 35xc2x0 C., preferably at about 20xc2x0 C. In step three, an aqueous solution of sodium acetate and hydroxylamine-O-sulfonic acid is added to provide the corresponding sulfonamide antiinflammatory agents 31 of this invention. Alternatively, the anion solutions generated in step one may be warmed to 0xc2x0 C. and treated with N-fluorodibenzenesulfonamide to provide the corresponding fluoromethyl sulfone antiinflammatory agents 32 of this invention. 
1-Phenyl-2-heterocycloimidazoles of the current invention 37 are synthesized by following the generic synthesis shown in Scheme XI. The reaction of a substituted heterocyclonitrile 33 with substituted anilines 34 (where Rb is as defined above for aryl and heteroaryl radicals) in the presence of alkylaluminum reagents such as trimethylaluminum, triethylaluminum, dimethylaluminum chloride, diethylaluminum chloride gives the amidine 35. The reaction of amidine 35 with a 2-halo-ketone derivative 18 (Xxe2x80x2=Br or Cl) in the presence of bases such as sodium bicarbonate, potassium carbonate, sodium carbonate, potassium bicarbonate or N,Nxe2x80x2-diisopropylethylamine gives the alkylated product 36. Some of the suitable solvents for this reaction are isopropanol, acetone and dimethylformamide. The reaction may be carried out at 20 to 90xc2x0 C. The intermediate 36 may be dehydrated in the presence of an acid catalyst such as 4-toluenesulfonic acid to give the targeted 1,2-diarylimidazoles 37. Suitable solvents for this dehydration step are e.g., toluene, xylene and benzene. Alternatively, trifluoroacetic acid may be used both as solvent and catalyst in this dehydration step. 
Scheme XII shows a two step method of forming sulfonyl anilines 39 from nitro compounds 38. In step one, the 4-methylthio-nitrobenzene 38 is oxidized to the sulfone with an oxidizing reagent such as hydrogen peroxide, potassium peroxymonosulfate (Oxone(copyright)) or 3-chloroperoxybenzoic acid (MCPBA). In step 2, the 4-methylsulfonyl-nitrobenzene is reduced to the corresponding aniline 39. 
Synthetic Scheme XIII describes an alternative method of forming 1-aryl-2-pyridyl-imidazoles 44 from 4-alkylthioanilines 40. The reaction of a substituted cyanopyridine 33 (where Ra is as defined above for aryl and heteroaryl radicals) with substituted anilines 40 in the presence of alkylaluminum reagents such as trimethylaluminum, triethylaluminum, dimethylaluminum chloride, diethylaluminum chloride gives the amidine 41. Alternatively, amidine 41 may be synthesized by reaction of aniline 40 first with a suitable base, and then with nitrile 33. Examples of suitable bases include sodium hydride, sodium methoxide, n-butyllithium and lithium diisopropylamide. These reactions may be run in solvents such as dimethyl sulfoxide, tetrahydrofuran, dimethoxyethane and methanol or the like. The reaction of amidine 41 with a 2-halo-ketone derivative 18 (Xxe2x80x2=Br or Cl) in the presence of bases such as sodium bicarbonate, potassium carbonate, sodium carbonate, potassium bicarbonate or N,Nxe2x80x2-diisopropylethylamine gives the alkylated product 42. Some of the suitable solvents for this reaction are isopropanol, acetone and dimethylformamide. The reaction may be carried out at 20 to 90xc2x0 C. The intermediate 42 is dehydrated in the presence of an acid catalyst such as 4-toluenesulfonic acid to give the 1-(4-alkylthio)aryl-2-pyridylimidazoles 43. Suitable solvents for this dehydration step are e.g., toluene, xylene and benzene. Oxidation of the alkylthio 43, with an oxidizing reagent such as hydrogen peroxide, Oxone(copyright) or MCPBA, yields the sulfones 44. 
Scheme XIV shows a method of forming sulfones and sulfonamides 46 from the corresponding 1-phenylimidazoles 45, where X is a leaving group such as halo. Treatment of 45 with base, such as butyl lithium, followed by addition of sulfur dioxide and a substituted alkyl or amine yields the corresponding sulfone or sulfonamide 46 (where Ra is alkyl or amino). 
Synthetic Scheme XV describes an alternative method of forming 1-aryl-2-pyridyl-imidazoles 53 from 4-nitrobenzenesulfonamide 47. Protection of 4-nitrobenzenesulfonamide 47, such as by reaction with acetonylacetone with p-toluenesulfonic acid as catalyst in a solvent such as toluene, forms the protected pyrrolylsulfonyl 48. A preferred protecting agent is 2,5-lower alkyl pyrrole, and more preferred is 2,5-dimethyl pyrrole. Reduction of the nitro compound 48, such as by Raney Nickel-catalyzed hydrogenation, yields the protected benzenamine 49. Amidine 50 is synthesized by reaction of benzenamine 49 first with a suitable base, and then with nitrile 33. Examples of suitable bases include sodium bis(trimethylsilyl)amide, sodium hydride, sodium methoxide, n-butyllithium and lithium diisopropylamide. This reaction may be run in solvents such as dimethyl sulfoxide, tetrahydrofuran, dimethoxyethane, methanol, or the like. The reaction of amidine 50 with a 2-halo-ketone derivative 18 (Xxe2x80x2=Br or Cl) in the presence of bases such as sodium bicarbonate, potassium carbonate, sodium carbonate, potassium bicarbonate or N,N-diisopropylethylamine gives the hydroxyimidazole 51. Some of the suitable solvents for this reaction are isopropanol, acetone and dimethylformamide. The reaction may be carried out at 20 to 90xc2x0 C. The intermediate 51 is dehydrated in the presence of an acid catalyst such as 4-toluenesulfonic acid to give the protected 1-(4-sulfonyl)aryl-imidazoles 52. Suitable solvents for this dehydration step are e.g., toluene, xylene and benzene. Acid deprotection of 52 such as with aqueous trifluoroacetic acid (TFA) at reflux temperature produces the sulfonamides 53.
The following currently pending applications are incorporated by reference: International Application PCT/US95/09506, patent application Ser. Nos. 08/464,154, and 08/282,395.
The following examples contain detailed descriptions of the methods of preparation of compounds of Formula I-V. These detailed descriptions fall within the scope, and serve to exemplify, the above described General Synthetic Procedures which form part of the invention. These detailed descriptions are presented for illustrative purposes only and are not intended as a restriction on the scope of the invention. All parts are by weight and temperatures are in Degrees centigrade unless otherwise indicated. All compounds showed NMR spectra consistent with their assigned structures. In some cases, the assigned structures were confirmed by nuclear Overhauser effect (NOE) experiments.